{ "$schema_version": "5.3", "review_mode": "fresh", "claim_restatement": { "index_wording": "Brain Microbiome Hypothesis", "entry_form": "phenomenon", "gradeable_restatement": "The living human brain harbors a resident microbial community that contributes causally to neurodegeneration.", "restatement_required": true, "split_into": [], "parent_claim": null, "scope_qualifiers": [ { "qualifier": "Species, living surgical versus postmortem tissue, clinical state, brain compartment, collection delay and analytical workflow", "determinable_before_outcome": true, "determined_from": "Enrollment and experimental design, before results; no responder-defined scope.", "action": "retained" } ] }, "hypothesis": { "name": "Brain Microbiome Hypothesis", "central_claim": "The living human brain harbors a resident microbial community that contributes causally to neurodegeneration.", "proposed_mechanism": "The living human brain harbors a resident microbial community that contributes causally to neurodegeneration.", "claimed_scope": "Resident viable communities in living human parenchyma, with infection, transient ingress, cadaver dynamics and teleost ecology treated separately.", "claimed_level": [ "initiation", "progression" ], "is_conjunctive": true, "conjunctive_note": "Existence of a resident human brain community is the index dominant gate. Separate endogenous residence from infection, transient entry, postmortem translocation and contamination. Downstream disease causality cannot establish residence. Animal/teleost results remain bounded comparators." }, "rubric_routing": { "primary_rubric": "04-microbiome-systemic.md", "secondary_rubrics": [ "01-neurodegeneration.md" ], "index_notes_applied": [ "Existence of a resident human brain community is the index dominant gate. Separate endogenous residence from infection, transient entry, postmortem translocation and contamination. Downstream disease causality cannot establish residence. Animal/teleost results remain bounded comparators." ], "rubric_fit_note": "Exact archived v5.3 framework. Any stale index empirical framing is rechecked against primary results." }, "subclaim_matrix": { "subclaims": [ { "id": "SC1", "statement": "Living human brain parenchyma contains a reproducible resident microbial community.", "subclaim_type": "existence", "scope": "healthy and diseased living human brains with preanalytic controls", "claimed_scope": "healthy and diseased living human brains with preanalytic controls", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Contamination-controlled quantitative orthogonal detection and viability", "hsef_level": "Α", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Α: orthogonal positive surgical/autopsy signals exist, but no independent viable strain-resolved living-human community replication excludes the demonstrated artifact alternatives. This is an unresolved existence gate, not a finding of universal sterility." }, { "id": "SC2", "statement": "The observed microbial signal exceeds reagent, host-mispriming, agonal and postmortem artifacts.", "subclaim_type": "mechanism", "scope": "matched batches and postmortem intervals", "claimed_scope": "matched batches and postmortem intervals", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Blanks, mock communities, host sequence checks and controlled sampling", "hsef_level": "Β", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Β: controls and edge/core comparisons improve specificity, but no complete human case rules out reagent, host, vascular and preanalytic origins together; host-aware null and assay-recovery failures constrain both directions." }, { "id": "SC3", "statement": "The resident community causally contributes to neurodegeneration.", "subclaim_type": "primacy", "scope": "defined human or disease-relevant resident-community settings", "claimed_scope": "defined human or disease-relevant resident-community settings", "governing_rubric": "04-microbiome-systemic.md", "key_evidence_anchor": "Strain-specific removal/rescue with meaningful disease endpoints", "hsef_level": "Γ", "confidence": "Moderate", "governing_cap_or_threshold": "Quoted boundary and upward audit below.", "rationale": "Γ: microbial products and installed infection can change relevant readouts, but resident-human community removal/rescue and neurodegenerative phenotype movement are absent from the examined corpus." } ], "aggregation_rule": "primary-subclaim", "aggregation_preregistered": true, "aggregation_rationale": "Existence of a resident human brain community is the index dominant gate. Separate endogenous residence from infection, transient entry, postmortem translocation and contamination. Downstream disease causality cannot establish residence. Animal/teleost results remain bounded comparators.", "primary_subclaim_id": "SC1", "aggregation_derivation": "Preregistered primary-subclaim aggregation returns Α because SC1 living-human community existence remains unresolved under the low-biomass contamination gate. SC2 Β and SC3 Γ do not replace that prerequisite. Weakest-link and scope-matched sensitivities also return Α. Positive fish ecology and AD autopsy culture are explicitly retained rather than dismissed.", "aggregation_alternatives": { "weakest_link_would_return": "Α", "primary_subclaim_would_return": "Α", "scope_matched_would_return": "Α", "note": "Separate narrow successes do not replace the preregistered gate." }, "index_rule_deviation": "" }, "competing_models": { "models_evaluated": [ { "rank_in_tournament": 1, "model_id": "M2", "is_nominal": false, "name": "Low-biomass reagent/host artifact", "core_claim": "Several technical sources can generate reproducible apparent bacterial profiles.", "explains_what_nominal_does_not": "Several technical sources can generate reproducible apparent bacterial profiles.", "strongest_supporting_evidence": [ "Host-off-target disease taxa, dilution/batch interventions and cross-contamination benchmarks: PMIDs 33771222, 25387460, 31164452, 31239396." ], "strongest_contradictory_evidence": [ "Positive surgical RNA/ISH, culture and edge/core patterns are not all explained away; method comparators are not universal brain nulls." ], "hsef_level_for_this_model": "Ε", "rationale": "Host-off-target disease taxa, dilution/batch interventions and cross-contamination benchmarks: PMIDs 33771222, 25387460, 31164452, 31239396. Positive surgical RNA/ISH, culture and edge/core patterns are not all explained away; method comparators are not universal brain nulls." }, { "rank_in_tournament": 2, "model_id": "M5", "is_nominal": false, "name": "Disease-related transient microbial ingress", "core_claim": "Pathogens or their molecules reach brain in selected disease settings without a stable community.", "explains_what_nominal_does_not": "Pathogens or their molecules reach brain in selected disease settings without a stable community.", "strongest_supporting_evidence": [ "Transient sepsis bacteria, HIV microbial molecules, AD Chlamydia isolates and installed P. gingivalis entry: PMIDs 29232157, 36202168, 18829386, 36631446." ], "strongest_contradictory_evidence": [ "Cannot explain all purported homeostatic signals or establish common sporadic neurodegeneration causality." ], "hsef_level_for_this_model": "Ε", "rationale": "Transient sepsis bacteria, HIV microbial molecules, AD Chlamydia isolates and installed P. gingivalis entry: PMIDs 29232157, 36202168, 18829386, 36631446. Cannot explain all purported homeostatic signals or establish common sporadic neurodegeneration causality." }, { "rank_in_tournament": 3, "model_id": "M4", "is_nominal": false, "name": "Teleost-restricted residency", "core_claim": "Healthy salmonid brain can contain viable bacteria under the reported conditions.", "explains_what_nominal_does_not": "Healthy salmonid brain can contain viable bacteria under the reported conditions.", "strongest_supporting_evidence": [ "Culture, perfusion, localization, negative controls and tagged colonization: PMID39292785." ], "strongest_contradictory_evidence": [ "Shared study/fish sources, limited long-term persistence and no human replication prevent broad extrapolation." ], "hsef_level_for_this_model": "Ε", "rationale": "Culture, perfusion, localization, negative controls and tagged colonization: PMID39292785. Shared study/fish sources, limited long-term persistence and no human replication prevent broad extrapolation." }, { "rank_in_tournament": 4, "model_id": "M3", "is_nominal": false, "name": "Agonal/postmortem translocation", "core_claim": "Cadaver communities and handling change tissue microbial signals.", "explains_what_nominal_does_not": "Cadaver communities and handling change tissue microbial signals.", "strongest_supporting_evidence": [ "Cadaver interval studies and two-cohort brain processing effects: PMIDs 25091187, 33363519, 32310171." ], "strongest_contradictory_evidence": [ "Long-delay cadavers cannot explain rapid surgical specimens by themselves." ], "hsef_level_for_this_model": "Δ", "rationale": "Cadaver interval studies and two-cohort brain processing effects: PMIDs 25091187, 33363519, 32310171. Long-delay cadavers cannot explain rapid surgical specimens by themselves." }, { "rank_in_tournament": 5, "model_id": "M1", "is_nominal": true, "name": "Resident human brain community", "core_claim": "A viable stable brain community contributes to neurodegeneration.", "explains_what_nominal_does_not": "A viable stable brain community contributes to neurodegeneration.", "strongest_supporting_evidence": [ "Surgical/autopsy RNA/ISH, positive AD culture and controlled taxonomic patterns: PMIDs 23355888, 18829386, 40284643." ], "strongest_contradictory_evidence": [ "No contamination-resistant independent viable living-human community replication or strain-specific disease removal/rescue." ], "hsef_level_for_this_model": "Α", "rationale": "Surgical/autopsy RNA/ISH, positive AD culture and controlled taxonomic patterns: PMIDs 23355888, 18829386, 40284643. No contamination-resistant independent viable living-human community replication or strain-specific disease removal/rescue." } ], "tournament_summary": "Descriptive comparison; does not modify the nominal score. Randomize aliquots from promptly collected living human surgical parenchyma across independent laboratories and extraction lots, with vascular, tool, kit, PCR, RNA, culture and spike-in controls. Joint strain-linked viability/localization beats a taxonomic signature.", "study_separating_rank1_from_rank2": "Randomize aliquots from promptly collected living human surgical parenchyma across independent laboratories and extraction lots, with vascular, tool, kit, PCR, RNA, culture and spike-in controls. Joint strain-linked viability/localization beats a taxonomic signature.", "nominal_wins_only_by_funding_artifact": false, "level_unchanged_by_tournament": true }, "evidence_inventory": [ { "n": 1, "pmid": "23355888", "title": "Brain microbial populations in HIV/AIDS: α-proteobacteria predominate independent of host immune status.", "citation": "Branton WG, Ellestad KK, Maingat F et al. Brain microbial populations in HIV/AIDS: α-proteobacteria predominate independent of host immune status. PloS one. 2013.", "doi": "10.1371/journal.pone.0054673", "pmcid": "PMC3552853", "url": "https://pubmed.ncbi.nlm.nih.gov/23355888/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/23355888/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID23355888", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph15, 1:Results:paragraph17, 1:Results:paragraph18, 1:Results:paragraph19, 1:Results:paragraph23, 1:Results:paragraph24, 3:Materials and Methods:paragraph4, 3:Materials and Methods:paragraph5, 3:Materials and Methods:paragraph10. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human tissue and forced mouse transfer", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Surgical epilepsy and autopsy brain show bacterial RNA, glial antigen/ISH and seven-week RNA recovery after implantation in Rag1-null mice, with PCR water and tool controls.", "what_it_does_not_show": "No human culture or resident-community disease phenotype; heated ODC13 and unheated ODC14 are different donors, confounding the viability contrast. SURG is epilepsy tissue, not healthy population sampling.", "confounders_present": [ "No human culture or resident-community disease phenotype; heated ODC13 and unheated ODC14 are different donors, confounding the viability contrast. SURG is epilepsy tissue, not healthy population sampling." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 2, "pmid": "33771222", "title": "Much ado about nothing? Off-target amplification can lead to false-positive bacterial brain microbiome detection in healthy and Parkinson's disease individuals.", "citation": "Bedarf JR, Beraza N, Khazneh H et al. Much ado about nothing? Off-target amplification can lead to false-positive bacterial brain microbiome detection in healthy and Parkinson's disease individuals. Microbiome. 2021.", "doi": "10.1186/s40168-021-01012-1", "pmcid": "PMC8004470", "url": "https://pubmed.ncbi.nlm.nih.gov/33771222/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33771222/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID33771222", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph15, 1:Methods:paragraph23, 1:Methods:paragraph26, 1:Methods:paragraph28, 2:Results:paragraph2, 2:Results:paragraph15, 2:Results:paragraph16, 2:Results:paragraph18, 2:Results:paragraph20, 2:Results:paragraph24, 2:Results:paragraph27, 2:Results:paragraph31. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "human brain and methodological controls", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "47 postmortem and three surgical samples were analyzed with extraction/PCR blanks, mock dilutions, qPCR and host alignment; disease-differentiating taxa were host off-targets.", "what_it_does_not_show": "Null is bounded to this assay/cohort. Positive mock missed Listeria and under-recovered Bacillus without mechanical lysis; residual human bacterial load was not literally zero.", "confounders_present": [ "Null is bounded to this assay/cohort. Positive mock missed Listeria and under-recovered Bacillus without mechanical lysis; residual human bacterial load was not literally zero." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 3, "pmid": "28676754", "title": "16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer's Post-Mortem Brain.", "citation": "Emery DC, Shoemark DK, Batstone TE et al. 16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer's Post-Mortem Brain. Frontiers in aging neuroscience. 2017.", "doi": "10.3389/fnagi.2017.00195", "pmcid": "PMC5476743", "url": "https://pubmed.ncbi.nlm.nih.gov/28676754/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28676754/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID28676754", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and Methods:paragraph0, 1:Materials and Methods:paragraph5, 1:Materials and Methods:paragraph6, 1:Materials and Methods:paragraph7, 1:Materials and Methods:paragraph11, 3:Discussion:paragraph0, 3:Discussion:paragraph2, 3:Discussion:paragraph3, 3:Discussion:paragraph9. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "AD temporal tissue yields more normalized 16S reads than controls; original Discussion acknowledges human 18S coamplification and possible secondary infection.", "what_it_does_not_show": "Normalized library read counts do not quantify absolute organisms or viability; age/postmortem matching cannot alone exclude reagent or host artifacts.", "confounders_present": [ "Normalized library read counts do not quantify absolute organisms or viability; age/postmortem matching cannot alone exclude reagent or host artifacts." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 4, "pmid": "36570533", "title": "High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer's and Parkinson's disease.", "citation": "Emery DC, Davies M, Cerajewska TL et al. High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer's and Parkinson's disease. Frontiers in aging neuroscience. 2022.", "doi": "10.3389/fnagi.2022.1026260", "pmcid": "PMC9780557", "url": "https://pubmed.ncbi.nlm.nih.gov/36570533/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36570533/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID36570533", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "High-resolution 16S profiling reports bacterial differences across AD/PD-associated brain regions and peripheral comparator tissues.", "what_it_does_not_show": "Taxonomic detection cannot establish living parenchymal residence, temporal direction or causal disease contribution; abstract-only controls.", "confounders_present": [ "Taxonomic detection cannot establish living parenchymal residence, temporal direction or causal disease contribution; abstract-only controls." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 5, "pmid": "40284643", "title": "Microspatial Heterogeneities and the Absence of Postmortem Contamination in Alzheimer's Disease Brain Microbiota: An Alzheimer's Pathobiome Initiative (AlzPI) Study.", "citation": "Thwe MN, Moné Y, Sen B et al. Microspatial Heterogeneities and the Absence of Postmortem Contamination in Alzheimer's Disease Brain Microbiota: An Alzheimer's Pathobiome Initiative (AlzPI) Study. Microorganisms. 2025.", "doi": "10.3390/microorganisms13040807", "pmcid": "PMC12029928", "url": "https://pubmed.ncbi.nlm.nih.gov/40284643/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/40284643/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID40284643", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:2. Materials and Methods:paragraph0, 1:2. Materials and Methods:paragraph4, 1:2. Materials and Methods:paragraph5, 1:2. Materials and Methods:paragraph6, 2:3. Results and Discussion:paragraph0, 2:3. Results and Discussion:paragraph3, 2:3. Results and Discussion:paragraph4, 2:3. Results and Discussion:paragraph6, 2:3. Results and Discussion:paragraph8. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human postmortem", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "86 samples from 31 specimens, 14 AD/17 controls, with four extraction blanks and edge/core sampling; no edge enrichment and some disease-associated taxa after decontamination.", "what_it_does_not_show": "No edge enrichment is not statistical equivalence or absence of all contamination; both edge and core may share reagent/intravascular sources. No culture or prospective disease ordering.", "confounders_present": [ "No edge enrichment is not statistical equivalence or absence of all contamination; both edge and core may share reagent/intravascular sources. No culture or prospective disease ordering." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 6, "pmid": "37780846", "title": "Evidence supportive of a bacterial component in the etiology for Alzheimer's disease and for a temporal-spatial development of a pathogenic microbiome in the brain.", "citation": "Moné Y, Earl JP, Król JE et al. Evidence supportive of a bacterial component in the etiology for Alzheimer's disease and for a temporal-spatial development of a pathogenic microbiome in the brain. Frontiers in cellular and infection microbiology. 2023.", "doi": "10.3389/fcimb.2023.1123228", "pmcid": "PMC10534976", "url": "https://pubmed.ncbi.nlm.nih.gov/37780846/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37780846/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID37780846", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and methods:paragraph0, 1:Materials and methods:paragraph25, 1:Materials and methods:paragraph44, 1:Materials and methods:paragraph49. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human postmortem computational", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "130 samples from 32 subjects and four extraction blanks support full-length 16S patterns; LDA extracts co-occurrence classes.", "what_it_does_not_show": "LDA classes are not organism abundance or measured longitudinal time. Ordering assumes health precedes disease; inferred stages do not establish microbial initiation.", "confounders_present": [ "LDA classes are not organism abundance or measured longitudinal time. Ordering assumes health precedes disease; inferred stages do not establish microbial initiation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 7, "pmid": "39061418", "title": "Regional Differences in Microbial Infiltration of Brain Tissue from Alzheimer's Disease Patients and Control Individuals.", "citation": "Jones TB, Chu P, Wilkey B et al. Regional Differences in Microbial Infiltration of Brain Tissue from Alzheimer's Disease Patients and Control Individuals. Brain sciences. 2024.", "doi": "10.3390/brainsci14070677", "pmcid": "PMC11274863", "url": "https://pubmed.ncbi.nlm.nih.gov/39061418/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39061418/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID39061418", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Bacterial products and microbial profiles vary by region in AD/control tissue, including widespread LPS immunoreactivity.", "what_it_does_not_show": "LPS indicates material, not viability, and region differences permit entry/clearance or handling explanations; original body not examined.", "confounders_present": [ "LPS indicates material, not viability, and region differences permit entry/clearance or handling explanations; original body not examined." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 8, "pmid": "31798558", "title": "Brain Microbiota in Huntington's Disease Patients.", "citation": "Alonso R, Pisa D, Carrasco L et al. Brain Microbiota in Huntington's Disease Patients. Frontiers in microbiology. 2019.", "doi": "10.3389/fmicb.2019.02622", "pmcid": "PMC6861841", "url": "https://pubmed.ncbi.nlm.nih.gov/31798558/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31798558/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID31798558", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Seven Huntington disease brains show fungal/bacterial structures and sequence signals across regions.", "what_it_does_not_show": "Same laboratory platforms recur; no contamination-resistant independent living-human community replication or causal intervention.", "confounders_present": [ "Same laboratory platforms recur; no contamination-resistant independent living-human community replication or causal intervention." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 9, "pmid": "26468932", "title": "Different Brain Regions are Infected with Fungi in Alzheimer's Disease.", "citation": "Pisa D, Alonso R, Rábano A et al. Different Brain Regions are Infected with Fungi in Alzheimer's Disease. Scientific reports. 2015.", "doi": "10.1038/srep15015", "pmcid": "PMC4606562", "url": "https://pubmed.ncbi.nlm.nih.gov/26468932/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26468932/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID26468932", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Ten AD brains show fungal-antibody immunoreactivity in different regions alongside sequence-based evidence.", "what_it_does_not_show": "Antibody structures and postmortem fungal DNA do not identify a reproducible viable community in living healthy brains.", "confounders_present": [ "Antibody structures and postmortem fungal DNA do not identify a reproducible viable community in living healthy brains." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 10, "pmid": "28387676", "title": "Identification of Fungal Species in Brain Tissue from Alzheimer's Disease by Next-Generation Sequencing.", "citation": "Alonso R, Pisa D, Aguado B et al. Identification of Fungal Species in Brain Tissue from Alzheimer's Disease by Next-Generation Sequencing. Journal of Alzheimer's disease : JAD. 2017.", "doi": "10.3233/JAD-170058", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/28387676/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28387676/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID28387676", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Fungal ITS sequencing in nine AD subjects identifies diverse species and regional differences.", "what_it_does_not_show": "Amplified low-biomass taxonomic signals require matched blanks and viability; relative diversity does not establish causality.", "confounders_present": [ "Amplified low-biomass taxonomic signals require matched blanks and viability; relative diversity does not establish causality." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 11, "pmid": "28717130", "title": "Polymicrobial Infections In Brain Tissue From Alzheimer's Disease Patients.", "citation": "Pisa D, Alonso R, Fernández-Fernández AM et al. Polymicrobial Infections In Brain Tissue From Alzheimer's Disease Patients. Scientific reports. 2017.", "doi": "10.1038/s41598-017-05903-y", "pmcid": "PMC5514053", "url": "https://pubmed.ncbi.nlm.nih.gov/28717130/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/28717130/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID28717130", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "AD tissue shows polymicrobial antibody/PCR signals; Borrelia/chlamydial antibodies cross-react and targeted Borrelia/HSV PCR is negative in the tested series.", "what_it_does_not_show": "Cross-reactive immunoreactivity cannot identify those pathogens; positive broad taxonomies and negative specific PCR test different targets.", "confounders_present": [ "Cross-reactive immunoreactivity cannot identify those pathogens; positive broad taxonomies and negative specific PCR test different targets." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 12, "pmid": "32174790", "title": "Parkinson's Disease: A Comprehensive Analysis of Fungi and Bacteria in Brain Tissue.", "citation": "Pisa D, Alonso R, Carrasco L et al. Parkinson's Disease: A Comprehensive Analysis of Fungi and Bacteria in Brain Tissue. International journal of biological sciences. 2020.", "doi": "10.7150/ijbs.42257", "pmcid": "PMC7053320", "url": "https://pubmed.ncbi.nlm.nih.gov/32174790/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32174790/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID32174790", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Six PD subjects show fungal and bacterial signals by immunohistology and sequencing.", "what_it_does_not_show": "Small postmortem series from recurring platform, without prospective viability or removal/rescue; disease-associated entry remains possible.", "confounders_present": [ "Small postmortem series from recurring platform, without prospective viability or removal/rescue; disease-associated entry remains possible." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 13, "pmid": "27013948", "title": "Corpora Amylacea of Brain Tissue from Neurodegenerative Diseases Are Stained with Specific Antifungal Antibodies.", "citation": "Pisa D, Alonso R, Rábano A et al. Corpora Amylacea of Brain Tissue from Neurodegenerative Diseases Are Stained with Specific Antifungal Antibodies. Frontiers in neuroscience. 2016.", "doi": "10.3389/fnins.2016.00086", "pmcid": "PMC4781869", "url": "https://pubmed.ncbi.nlm.nih.gov/27013948/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27013948/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID27013948", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Corpora amylacea from several neurodegenerative diseases stain with antifungal antibodies.", "what_it_does_not_show": "Storage/clearance bodies and antigens do not demonstrate live microbes or disease-specific causal residence.", "confounders_present": [ "Storage/clearance bodies and antigens do not demonstrate live microbes or disease-specific causal residence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 14, "pmid": "25892962", "title": "Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis.", "citation": "Alonso R, Pisa D, Marina AI et al. Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis. International journal of biological sciences. 2015.", "doi": "10.7150/ijbs.11084", "pmcid": "PMC4400386", "url": "https://pubmed.ncbi.nlm.nih.gov/25892962/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25892962/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID25892962", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human CSF and postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "ALS CSF and brain contain fungal protein/DNA signals in reported assays.", "what_it_does_not_show": "CSF and postmortem products are not living parenchymal community evidence; no phenotype-specific eradication.", "confounders_present": [ "CSF and postmortem products are not living parenchymal community evidence; no phenotype-specific eradication." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 15, "pmid": "25125470", "title": "Direct visualization of fungal infection in brains from patients with Alzheimer's disease.", "citation": "Pisa D, Alonso R, Juarranz A et al. Direct visualization of fungal infection in brains from patients with Alzheimer's disease. Journal of Alzheimer's disease : JAD. 2015.", "doi": "10.3233/JAD-141386", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/25125470/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25125470/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID25125470", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem and infected animal comparator", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Intracellular fungal-like staining occurs in AD neurons, compared with experimentally Candida-infected animals.", "what_it_does_not_show": "Infected-animal morphology supports assay plausibility but cannot identify viable human species or distinguish nonspecific staining.", "confounders_present": [ "Infected-animal morphology supports assay plausibility but cannot identify viable human species or distinguish nonspecific staining." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 16, "pmid": "27872620", "title": "Fungal Enolase, β-Tubulin, and Chitin Are Detected in Brain Tissue from Alzheimer's Disease Patients.", "citation": "Pisa D, Alonso R, Rábano A et al. Fungal Enolase, β-Tubulin, and Chitin Are Detected in Brain Tissue from Alzheimer's Disease Patients. Frontiers in microbiology. 2016.", "doi": "10.3389/fmicb.2016.01772", "pmcid": "PMC5097921", "url": "https://pubmed.ncbi.nlm.nih.gov/27872620/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27872620/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID27872620", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Fungal enolase, tubulin and chitin antibody signals appear in AD tissue, with some control positives and chitin-negative corpora amylacea.", "what_it_does_not_show": "Multiple antigens are not culture or a strain-resolved community; heterogeneous negative/positive structures limit specificity.", "confounders_present": [ "Multiple antigens are not culture or a strain-resolved community; heterogeneous negative/positive structures limit specificity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 17, "pmid": "29881346", "title": "Infection of Fungi and Bacteria in Brain Tissue From Elderly Persons and Patients With Alzheimer's Disease.", "citation": "Alonso R, Pisa D, Fernández-Fernández AM et al. Infection of Fungi and Bacteria in Brain Tissue From Elderly Persons and Patients With Alzheimer's Disease. Frontiers in aging neuroscience. 2018.", "doi": "10.3389/fnagi.2018.00159", "pmcid": "PMC5976758", "url": "https://pubmed.ncbi.nlm.nih.gov/29881346/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29881346/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID29881346", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and Methods:paragraph1, 1:Materials and Methods:paragraph4, 1:Materials and Methods:paragraph5, 1:Materials and Methods:paragraph8, 1:Materials and Methods:paragraph9. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Fungal/bacterial profiling reports AD-control differences; original Methods describe rapid autopsy, sterile sampling and multiple PCR negatives.", "what_it_does_not_show": "Negatives are documented, contrary to a blanket absent-controls claim. Methods examined do not establish independent sequenced bacterial extraction blanks, quantitative load, host screening or viability.", "confounders_present": [ "Negatives are documented, contrary to a blanket absent-controls claim. Methods examined do not establish independent sequenced bacterial extraction blanks, quantitative load, host screening or viability." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 18, "pmid": "29959356", "title": "Human and Microbial Proteins From Corpora Amylacea of Alzheimer's Disease.", "citation": "Pisa D, Alonso R, Marina AI et al. Human and Microbial Proteins From Corpora Amylacea of Alzheimer's Disease. Scientific reports. 2018.", "doi": "10.1038/s41598-018-28231-1", "pmcid": "PMC6026157", "url": "https://pubmed.ncbi.nlm.nih.gov/29959356/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29959356/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID29959356", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem proteomic", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Two AD corpora-amylacea preparations contain reported microbial and host proteins, with DNA assays supporting fungal signals.", "what_it_does_not_show": "Protein attribution in small selected preparations does not establish living microbial residence or its necessity for disease.", "confounders_present": [ "Protein attribution in small selected preparations does not establish living microbial residence or its necessity for disease." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 19, "pmid": "26401766", "title": "Cerebrospinal Fluid from Alzheimer's Disease Patients Contains Fungal Proteins and DNA.", "citation": "Alonso R, Pisa D, Rábano A et al. Cerebrospinal Fluid from Alzheimer's Disease Patients Contains Fungal Proteins and DNA. Journal of Alzheimer's disease : JAD. 2015.", "doi": "10.3233/JAD-150382", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/26401766/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/26401766/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID26401766", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human CSF", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "AD CSF slot-blot/PCR assays report fungal material.", "what_it_does_not_show": "Fluid material need not reflect a viable parenchymal community; assay contamination and specificity need original control scrutiny.", "confounders_present": [ "Fluid material need not reflect a viable parenchymal community; assay contamination and specificity need original control scrutiny." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 20, "pmid": "24614898", "title": "Fungal infection in patients with Alzheimer's disease.", "citation": "Alonso R, Pisa D, Marina AI et al. Fungal infection in patients with Alzheimer's disease. Journal of Alzheimer's disease : JAD. 2014.", "doi": "10.3233/JAD-132681", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/24614898/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/24614898/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID24614898", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem proteomic", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "AD specimens show fungal protein/PCR signals interpreted as infection.", "what_it_does_not_show": "Molecules can persist after clearance or enter from elsewhere; infection is distinct from a stable resident community.", "confounders_present": [ "Molecules can persist after clearance or enter from elsewhere; infection is distinct from a stable resident community." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 21, "pmid": "27784770", "title": "Gram-negative bacterial molecules associate with Alzheimer disease pathology.", "citation": "Zhan X, Stamova B, Jin LW et al. Gram-negative bacterial molecules associate with Alzheimer disease pathology. Neurology. 2016.", "doi": "10.1212/WNL.0000000000003391", "pmcid": "PMC5135029", "url": "https://pubmed.ncbi.nlm.nih.gov/27784770/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27784770/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID27784770", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "24 AD and 18 control brains contain LPS/E. coli K99 immunoreactivity, with stronger signals associated with AD pathology.", "what_it_does_not_show": "Control positivity and pathology correlation do not establish viable bacteria, causal direction or resident-community necessity.", "confounders_present": [ "Control positivity and pathology correlation do not establish viable bacteria, causal direction or resident-community necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 22, "pmid": "29232157", "title": "Bacterial Dissemination to the Brain in Sepsis.", "citation": "Singer BH, Dickson RP, Denstaedt SJ et al. Bacterial Dissemination to the Brain in Sepsis. American journal of respiratory and critical care medicine. 2018.", "doi": "10.1164/rccm.201708-1559OC", "pmcid": "PMC5855074", "url": "https://pubmed.ncbi.nlm.nih.gov/29232157/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/29232157/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID29232157", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human sepsis and animal sepsis", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Sepsis mice have viable brain bacteria around day five but not day 14; human postmortem sepsis brain signals correlate with the systemic source.", "what_it_does_not_show": "Demonstrates transient disease-associated dissemination, not homeostatic residency or sporadic neurodegenerative causality.", "confounders_present": [ "Demonstrates transient disease-associated dissemination, not homeostatic residency or sporadic neurodegenerative causality." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 23, "pmid": "39292785", "title": "A brain microbiome in salmonids at homeostasis.", "citation": "Mani A, Henn C, Couch C et al. A brain microbiome in salmonids at homeostasis. Science advances. 2024.", "doi": "10.1126/sciadv.ado0277", "pmcid": "PMC11409976", "url": "https://pubmed.ncbi.nlm.nih.gov/39292785/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39292785/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID39292785", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph0, 1:RESULTS:paragraph2, 1:RESULTS:paragraph3, 1:RESULTS:paragraph10, 1:RESULTS:paragraph15, 1:RESULTS:paragraph16, 1:RESULTS:paragraph24. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2", "SC3" ], "favors_models": [], "evidence_class": "Strong", "system": "teleost homeostasis and exposure", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Perfused trout brains show RNA/DNA, localized bacteria and 54 cultured isolates; buffer/CSF negatives, environment controls, antibiotics and tagged strain colonization corroborate fish residence.", "what_it_does_not_show": "Not human evidence. Tagged-strain persistence declines by day 14, brain isolates come from two fish for genome comparisons, and adult salmon LPS/amyloid association is not a causal degeneration intervention.", "confounders_present": [ "Not human evidence. Tagged-strain persistence declines by day 14, brain isolates come from two fish for genome comparisons, and adult salmon LPS/amyloid association is not a causal degeneration intervention." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 24, "pmid": "34908504", "title": "Cerebrospinal Fluid from Healthy Pregnant Women Does Not Harbor a Detectable Microbial Community.", "citation": "Kang Y, Ji X, Guo L et al. Cerebrospinal Fluid from Healthy Pregnant Women Does Not Harbor a Detectable Microbial Community. Microbiology spectrum. 2021.", "doi": "10.1128/Spectrum.00769-21", "pmcid": "PMC8672898", "url": "https://pubmed.ncbi.nlm.nih.gov/34908504/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34908504/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID34908504", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human CSF control study", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "23 healthy pregnant women, 116 CSF/control samples and paired metatranscriptomics show no active viable microbial community after contamination correction.", "what_it_does_not_show": "CSF is a distinct compartment and pregnancy a restricted population; cannot prove universal absence of parenchymal organisms.", "confounders_present": [ "CSF is a distinct compartment and pregnancy a restricted population; cannot prove universal absence of parenchymal organisms." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 25, "pmid": "25091187", "title": "Distinctive thanatomicrobiome signatures found in the blood and internal organs of humans.", "citation": "Can I, Javan GT, Pozhitkov AE et al. Distinctive thanatomicrobiome signatures found in the blood and internal organs of humans. Journal of microbiological methods. 2014.", "doi": "10.1016/j.mimet.2014.07.026", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/25091187/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25091187/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID25091187", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human cadaver comparator", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Four cadavers show tissue-specific postmortem microbial profiles and extraction-related differences.", "what_it_does_not_show": "Postmortem presence cannot be back-extrapolated to living residence; tiny comparator does not explain every brain signal.", "confounders_present": [ "Postmortem presence cannot be back-extrapolated to living residence; tiny comparator does not explain every brain signal." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 26, "pmid": "33363519", "title": "Effects of Extended Postmortem Interval on Microbial Communities in Organs of the Human Cadaver.", "citation": "Lutz H, Vangelatos A, Gottel N et al. Effects of Extended Postmortem Interval on Microbial Communities in Organs of the Human Cadaver. Frontiers in microbiology. 2020.", "doi": "10.3389/fmicb.2020.569630", "pmcid": "PMC7752770", "url": "https://pubmed.ncbi.nlm.nih.gov/33363519/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33363519/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID33363519", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human cadaver comparator", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "40 cadavers sampled over 24–432 hours show organ- and postmortem-interval-associated communities.", "what_it_does_not_show": "Long-delay autopsy dynamics do not imply all rapid-autopsy or surgical positives are postmortem invasion.", "confounders_present": [ "Long-delay autopsy dynamics do not imply all rapid-autopsy or surgical positives are postmortem invasion." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 27, "pmid": "32310171", "title": "Investigation of Potential Brain Microbiome in Alzheimer's Disease: Implications of Study Bias.", "citation": "Westfall S, Dinh DM, Pasinetti GM et al. Investigation of Potential Brain Microbiome in Alzheimer's Disease: Implications of Study Bias. Journal of Alzheimer's disease : JAD. 2020.", "doi": "10.3233/JAD-191328", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32310171/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32310171/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID32310171", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human postmortem replicated cohorts", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Two AD cohorts show processing/postmortem effects greater than the limited AD-control differences.", "what_it_does_not_show": "DNA may still be present; the null concerns disease signatures and study bias, not an absolute sterility proof.", "confounders_present": [ "DNA may still be present; the null concerns disease signatures and study bias, not an absolute sterility proof." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 28, "pmid": "36202168", "title": "Microbial molecule ingress promotes neuroinflammation and brain CCR5 expression in persons with HIV-associated neurocognitive disorders.", "citation": "Branton WG, Fernandes JP, Mohammadzadeh N et al. Microbial molecule ingress promotes neuroinflammation and brain CCR5 expression in persons with HIV-associated neurocognitive disorders. Brain, behavior, and immunity. 2023.", "doi": "10.1016/j.bbi.2022.09.019", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/36202168/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36202168/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID36202168", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human HIV and animal/cell comparators", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "22 HIV/11 control human and 11 SIV/4 control primate specimens show microbial molecules; peptidoglycan alters CCR5/HIV and neuronal mitochondrial readouts.", "what_it_does_not_show": "Translocated microbial molecules can act without resident viable bacteria; HIV-linked immune/barrier pathology is not sporadic neurodegeneration. Online 2022, issue 2023.", "confounders_present": [ "Translocated microbial molecules can act without resident viable bacteria; HIV-linked immune/barrier pathology is not sporadic neurodegeneration. Online 2022, issue 2023." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 29, "pmid": "25387460", "title": "Reagent and laboratory contamination can critically impact sequence-based microbiome analyses.", "citation": "Salter SJ, Cox MJ, Turek EM et al. Reagent and laboratory contamination can critically impact sequence-based microbiome analyses. BMC biology. 2014.", "doi": "10.1186/s12915-014-0087-z", "pmcid": "PMC4228153", "url": "https://pubmed.ncbi.nlm.nih.gov/25387460/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25387460/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID25387460", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph4, 1:Results:paragraph8, 1:Results:paragraph9, 1:Results:paragraph10, 1:Results:paragraph11, 1:Results:paragraph13. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Serial pure-culture dilutions across three facilities and multiple kits produce kit-specific false profiles; cohort-age clustering tracked kit batches.", "what_it_does_not_show": "Demonstrates a causal artifact mechanism, not proof that every positive human brain signal is contaminated; tested quantitative floors are protocol-specific.", "confounders_present": [ "Demonstrates a causal artifact mechanism, not proof that every positive human brain signal is contaminated; tested quantitative floors are protocol-specific." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 30, "pmid": "30887686", "title": "Laboratory contamination over time during low-biomass sample analysis.", "citation": "Weyrich LS, Farrer AG, Eisenhofer R et al. Laboratory contamination over time during low-biomass sample analysis. Molecular ecology resources. 2019.", "doi": "10.1111/1755-0998.13011", "pmcid": "PMC6850301", "url": "https://pubmed.ncbi.nlm.nih.gov/30887686/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30887686/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID30887686", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "144 negative controls over five years show kit/laboratory/researcher/month variation in contaminant communities.", "what_it_does_not_show": "A historical contaminant list cannot classify every future tissue taxon; this is methods evidence, not direct human-brain absence.", "confounders_present": [ "A historical contaminant list cannot classify every future tissue taxon; this is methods evidence, not direct human-brain absence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 31, "pmid": "32046792", "title": "Separating the signal from the noise in metagenomic cell-free DNA sequencing.", "citation": "Burnham P, Gomez-Lopez N, Heyang M et al. Separating the signal from the noise in metagenomic cell-free DNA sequencing. Microbiome. 2020.", "doi": "10.1186/s40168-020-0793-4", "pmcid": "PMC7014780", "url": "https://pubmed.ncbi.nlm.nih.gov/32046792/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32046792/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID32046792", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "computational methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Low-biomass metagenomic decontamination uses coverage and batch variation and is tested in clinical cfDNA settings.", "what_it_does_not_show": "Algorithmic benchmarking in urine/amniotic settings does not measure brain viability or guarantee filtering accuracy there.", "confounders_present": [ "Algorithmic benchmarking in urine/amniotic settings does not measure brain viability or guarantee filtering accuracy there." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 32, "pmid": "31412780", "title": "Laboratory contamination in airway microbiome studies.", "citation": "Drengenes C, Wiker HG, Kalananthan T et al. Laboratory contamination in airway microbiome studies. BMC microbiology. 2019.", "doi": "10.1186/s12866-019-1560-1", "pmcid": "PMC6694601", "url": "https://pubmed.ncbi.nlm.nih.gov/31412780/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31412780/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID31412780", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "airway methodological comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "23-subject airway study attributes substantial low-biomass profiles to laboratory contamination.", "what_it_does_not_show": "Airway-specific fractions do not estimate the brain fraction; matched brain recovery controls remain necessary.", "confounders_present": [ "Airway-specific fractions do not estimate the brain fraction; matched brain recovery controls remain necessary." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 33, "pmid": "34162397", "title": "Detection of cell-free microbial DNA using a contaminant-controlled analysis framework.", "citation": "Zozaya-Valdés E, Wong SQ, Raleigh J et al. Detection of cell-free microbial DNA using a contaminant-controlled analysis framework. Genome biology. 2021.", "doi": "10.1186/s13059-021-02401-3", "pmcid": "PMC8220693", "url": "https://pubmed.ncbi.nlm.nih.gov/34162397/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34162397/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID34162397", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "blood cfDNA methodological comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "A contaminant-controlled workflow detects microbial cfDNA exceeding blanks in plasma samples.", "what_it_does_not_show": "Circulating DNA can exist without live resident plasma organisms and may contribute to brain tissue signals.", "confounders_present": [ "Circulating DNA can exist without live resident plasma organisms and may contribute to brain tissue signals." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 34, "pmid": "32518181", "title": "Critical Relevance of Stochastic Effects on Low-Bacterial-Biomass 16S rRNA Gene Analysis.", "citation": "Erb-Downward JR, Falkowski NR, D'Souza JC et al. Critical Relevance of Stochastic Effects on Low-Bacterial-Biomass 16S rRNA Gene Analysis. mBio. 2020.", "doi": "10.1128/mBio.00258-20", "pmcid": "PMC7373192", "url": "https://pubmed.ncbi.nlm.nih.gov/32518181/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32518181/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID32518181", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Mock serial dilutions and clinical respiratory samples reveal stochastic profiles below the tested bacterial-load range.", "what_it_does_not_show": "The numerical copy threshold is assay-specific and cannot be imposed as a universal brain cutoff.", "confounders_present": [ "The numerical copy threshold is assay-specific and cannot be imposed as a universal brain cutoff." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 35, "pmid": "34834931", "title": "Metagenomic Identification of Viral Sequences in Laboratory Reagents.", "citation": "Porter AF, Cobbin J, Li CX et al. Metagenomic Identification of Viral Sequences in Laboratory Reagents. Viruses. 2021.", "doi": "10.3390/v13112122", "pmcid": "PMC8625350", "url": "https://pubmed.ncbi.nlm.nih.gov/34834931/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34834931/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID34834931", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Seven blank libraries contain 14 viral contaminants, demonstrating reagent-derived RNA/viral reads.", "what_it_does_not_show": "RNA detection alone cannot establish viability, but contamination in these reagents is not a universal explanation of all viral tissue findings.", "confounders_present": [ "RNA detection alone cannot establish viability, but contamination in these reagents is not a universal explanation of all viral tissue findings." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 36, "pmid": "37784008", "title": "HoCoRT: host contamination removal tool.", "citation": "Rumbavicius I, Rounge TB, Rognes T et al. HoCoRT: host contamination removal tool. BMC bioinformatics. 2023.", "doi": "10.1186/s12859-023-05492-w", "pmcid": "PMC10544359", "url": "https://pubmed.ncbi.nlm.nih.gov/37784008/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37784008/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID37784008", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "computational methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Synthetic/public benchmarks assess host-removal accuracy; long-read performance remains incomplete.", "what_it_does_not_show": "A host-removal tool is not direct biological evidence for or against brain residence.", "confounders_present": [ "A host-removal tool is not direct biological evidence for or against brain residence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 37, "pmid": "33382980", "title": "The cancer microbiome atlas: a pan-cancer comparative analysis to distinguish tissue-resident microbiota from contaminants.", "citation": "Dohlman AB, Arguijo Mendoza D, Ding S et al. The cancer microbiome atlas: a pan-cancer comparative analysis to distinguish tissue-resident microbiota from contaminants. Cell host & microbe. 2021.", "doi": "10.1016/j.chom.2020.12.001", "pmcid": "PMC7878430", "url": "https://pubmed.ncbi.nlm.nih.gov/33382980/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/33382980/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID33382980", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "cancer methodological comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Pan-cancer profiles use center/batch and matched tissue information to distinguish candidate tissue signals from contaminants.", "what_it_does_not_show": "Cancer/mucosal tissue validation does not establish brain microbiota or living strain identity.", "confounders_present": [ "Cancer/mucosal tissue validation does not establish brain microbiota or living strain identity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 38, "pmid": "25944184", "title": "CS-SCORE: Rapid identification and removal of human genome contaminants from metagenomic datasets.", "citation": "Haque MM, Bose T, Dutta A et al. CS-SCORE: Rapid identification and removal of human genome contaminants from metagenomic datasets. Genomics. 2015.", "doi": "10.1016/j.ygeno.2015.04.005", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/25944184/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/25944184/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID25944184", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "computational methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "CS-SCORE benchmarks human-read removal with computational efficiency benefits.", "what_it_does_not_show": "Speed and genome filtering do not certify low-copy bacterial identification, tissue localization or viability.", "confounders_present": [ "Speed and genome filtering do not certify low-copy bacterial identification, tissue localization or viability." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 39, "pmid": "36357382", "title": "De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee.", "citation": "Liu Y, Elworth RAL, Jochum MD et al. De novo identification of microbial contaminants in low microbial biomass microbiomes with Squeegee. Nature communications. 2022.", "doi": "10.1038/s41467-022-34409-z", "pmcid": "PMC9649624", "url": "https://pubmed.ncbi.nlm.nih.gov/36357382/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36357382/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID36357382", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "computational methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Squeegee cross-sample contaminant identification is benchmarked against control-based approaches.", "what_it_does_not_show": "Data-driven decontamination does not replace independent physical blanks or prove brain community existence.", "confounders_present": [ "Data-driven decontamination does not replace independent physical blanks or prove brain community existence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 40, "pmid": "32828122", "title": "Protoblock - A biological standard for formalin fixed samples.", "citation": "Flores Bueso Y, Walker SP, Hogan G et al. Protoblock - A biological standard for formalin fixed samples. Microbiome. 2020.", "doi": "10.1186/s40168-020-00901-1", "pmcid": "PMC7443293", "url": "https://pubmed.ncbi.nlm.nih.gov/32828122/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32828122/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID32828122", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Defined mammalian/bacterial FFPE blocks compare recovery with qPCR, 16S and whole-genome methods.", "what_it_does_not_show": "Useful assay recovery standard; fixed mock blocks are not viable organisms in human brain.", "confounders_present": [ "Useful assay recovery standard; fixed mock blocks are not viable organisms in human brain." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 41, "pmid": "30558668", "title": "Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data.", "citation": "Davis NM, Proctor DM, Holmes SP et al. Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome. 2018.", "doi": "10.1186/s40168-018-0605-2", "pmcid": "PMC6298009", "url": "https://pubmed.ncbi.nlm.nih.gov/30558668/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30558668/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID30558668", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "computational and experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "decontam uses frequency/prevalence with culture dilution and biological cohorts to identify contaminants.", "what_it_does_not_show": "Model assumptions can fail with cross-contamination or shared true/background taxa; filtered signal is not automatically true residence.", "confounders_present": [ "Model assumptions can fail with cross-contamination or shared true/background taxa; filtered signal is not automatically true residence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 42, "pmid": "31164452", "title": "Controlling for Contaminants in Low-Biomass 16S rRNA Gene Sequencing Experiments.", "citation": "Karstens L, Asquith M, Davin S et al. Controlling for Contaminants in Low-Biomass 16S rRNA Gene Sequencing Experiments. mSystems. 2019.", "doi": "10.1128/mSystems.00290-19", "pmcid": "PMC6550369", "url": "https://pubmed.ncbi.nlm.nih.gov/31164452/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31164452/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID31164452", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph12, 1:RESULTS:paragraph17, 1:RESULTS:paragraph18, 1:RESULTS:paragraph20, 1:RESULTS:paragraph22, 1:RESULTS:paragraph25. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Known mock dilutions quantify contamination and false deletion; blank-only filtering removes 20.1–33.9% of true ASVs and misses many contaminants.", "what_it_does_not_show": "No algorithm is perfect across mixtures. Unknown-source SourceTracker fails substantially, while known-source success cannot be assumed for brain.", "confounders_present": [ "No algorithm is perfect across mixtures. Unknown-source SourceTracker fails substantially, while known-source success cannot be assumed for brain." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 43, "pmid": "27107811", "title": "Decontamination of 16S rRNA gene amplicon sequence datasets based on bacterial load assessment by qPCR.", "citation": "Lazarevic V, Gaïa N, Girard M et al. Decontamination of 16S rRNA gene amplicon sequence datasets based on bacterial load assessment by qPCR. BMC microbiology. 2016.", "doi": "10.1186/s12866-016-0689-4", "pmcid": "PMC4842273", "url": "https://pubmed.ncbi.nlm.nih.gov/27107811/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27107811/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID27107811", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "qPCR bacterial-load-aware removal preserves known culture members and reduces tested contaminants.", "what_it_does_not_show": "Some sample cross-contaminants escape blank-based correction; recovery must be tested for the actual brain protocol.", "confounders_present": [ "Some sample cross-contaminants escape blank-based correction; recovery must be tested for the actual brain protocol." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 44, "pmid": "38145697", "title": "Alternative amplicon-PCR protocol for maximizing bacterial and fungal sequencing in low-biomass samples.", "citation": "Merker Breyer G, De Carli S, Rocha Jacques Da Silva ME et al. Alternative amplicon-PCR protocol for maximizing bacterial and fungal sequencing in low-biomass samples. Analytical biochemistry. 2024.", "doi": "10.1016/j.ab.2023.115449", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/38145697/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/38145697/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID38145697", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Alternative two-stage 16S/ITS amplification improves low-biomass sequencing in mocks and clinical samples.", "what_it_does_not_show": "Amplification yield or consistency cannot demonstrate microbial viability or absence of stochastic errors below recovery limits.", "confounders_present": [ "Amplification yield or consistency cannot demonstrate microbial viability or absence of stochastic errors below recovery limits." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 45, "pmid": "27688978", "title": "Validation of picogram- and femtogram-input DNA libraries for microscale metagenomics.", "citation": "Rinke C, Low S, Woodcroft BJ et al. Validation of picogram- and femtogram-input DNA libraries for microscale metagenomics. PeerJ. 2016.", "doi": "10.7717/peerj.2486", "pmcid": "PMC5036114", "url": "https://pubmed.ncbi.nlm.nih.gov/27688978/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/27688978/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID27688978", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "54-species mock and environmental microsamples validate very-low-input shotgun libraries with explicit complexity/contamination limits.", "what_it_does_not_show": "Real microspatial variation is possible; low-input validation in known communities is not automatic brain validity.", "confounders_present": [ "Real microspatial variation is possible; low-input validation in known communities is not automatic brain validity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 46, "pmid": "31239396", "title": "Quantifying and Understanding Well-to-Well Contamination in Microbiome Research.", "citation": "Minich JJ, Sanders JG, Amir A et al. Quantifying and Understanding Well-to-Well Contamination in Microbiome Research. mSystems. 2019.", "doi": "10.1128/mSystems.00186-19", "pmcid": "PMC6593221", "url": "https://pubmed.ncbi.nlm.nih.gov/31239396/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/31239396/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID31239396", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Unique bacterial assignments across two laboratories reveal well-to-well contamination, strongest at low biomass.", "what_it_does_not_show": "Cross-contamination can introduce real tissue taxa into blanks; blanket deletion of blank taxa can therefore erase true organisms.", "confounders_present": [ "Cross-contamination can introduce real tissue taxa into blanks; blanket deletion of blank taxa can therefore erase true organisms." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 47, "pmid": "34101489", "title": "Managing Contamination and Diverse Bacterial Loads in 16S rRNA Deep Sequencing of Clinical Samples: Implications of the Law of Small Numbers.", "citation": "Dyrhovden R, Rippin M, Øvrebø KK et al. Managing Contamination and Diverse Bacterial Loads in 16S rRNA Deep Sequencing of Clinical Samples: Implications of the Law of Small Numbers. mBio. 2021.", "doi": "10.1128/mBio.00598-21", "pmcid": "PMC8262989", "url": "https://pubmed.ncbi.nlm.nih.gov/34101489/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/34101489/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID34101489", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Mock and bile analyses with repeated controls show stochastic amplification and incomplete single-blank coverage.", "what_it_does_not_show": "Clinical bile is not brain; quantitative per-sample decision rules require protocol-specific recovery rather than taxon blacklists.", "confounders_present": [ "Clinical bile is not brain; quantitative per-sample decision rules require protocol-specific recovery rather than taxon blacklists." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 48, "pmid": "30801029", "title": "Performance of Microbiome Sequence Inference Methods in Environments with Varying Biomass.", "citation": "Caruso V, Song X, Asquith M et al. Performance of Microbiome Sequence Inference Methods in Environments with Varying Biomass. mSystems. 2019.", "doi": "10.1128/mSystems.00163-18", "pmcid": "PMC6381225", "url": "https://pubmed.ncbi.nlm.nih.gov/30801029/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30801029/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID30801029", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "computational methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Six inference approaches across biomass dilutions compare false sequence/OTU calls; ASV methods improve precision.", "what_it_does_not_show": "Sequence inference does not by itself distinguish true low-load tissue biology from contamination.", "confounders_present": [ "Sequence inference does not by itself distinguish true low-load tissue biology from contamination." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 49, "pmid": "30383890", "title": "Identification and removal of contaminating microbial DNA from PCR reagents: impact on low-biomass microbiome analyses.", "citation": "Stinson LF, Keelan JA, Payne MS et al. Identification and removal of contaminating microbial DNA from PCR reagents: impact on low-biomass microbiome analyses. Letters in applied microbiology. 2019.", "doi": "10.1111/lam.13091", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/30383890/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30383890/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID30383890", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "experimental methods comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "DNase treatment of PCR master mixes reduces measured reagent contamination about 99% in the tested protocol.", "what_it_does_not_show": "Kit extraction is not always the largest contaminant source; treatment must preserve assay sensitivity. Online 2018, issue 2019.", "confounders_present": [ "Kit extraction is not always the largest contaminant source; treatment must preserve assay sensitivity. Online 2018, issue 2019." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 50, "pmid": "32244052", "title": "Molecular diagnosis of polymicrobial brain abscesses with 16S-rDNA-based next-generation sequencing.", "citation": "Stebner A, Ensser A, Geißdörfer W et al. Molecular diagnosis of polymicrobial brain abscesses with 16S-rDNA-based next-generation sequencing. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2021.", "doi": "10.1016/j.cmi.2020.03.028", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/32244052/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32244052/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID32244052", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "human infection diagnostic comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "79 samples from 54 patients include 51 intracranial abscesses, with sequencing detecting broader polymicrobial pathogens.", "what_it_does_not_show": "Diagnostic infection is a positive assay control, not evidence of a normal resident human brain community.", "confounders_present": [ "Diagnostic infection is a positive assay control, not evidence of a normal resident human brain community." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 51, "pmid": "37741170", "title": "Identification of bacterial pathogens in brain abscesses by metagenomic approach using nanopore 16S amplicon sequencing.", "citation": "Son H, Moon J, Ha EJ et al. Identification of bacterial pathogens in brain abscesses by metagenomic approach using nanopore 16S amplicon sequencing. Diagnostic microbiology and infectious disease. 2023.", "doi": "10.1016/j.diagmicrobio.2023.116041", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/37741170/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/37741170/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID37741170", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human infection diagnostic comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Nanopore 16S of 27 abscess pus samples detects more anaerobic/polymicrobial findings than culture.", "what_it_does_not_show": "Abscess load, inflammation and collection differ from healthy low-biomass brain; detection is not homeostasis.", "confounders_present": [ "Abscess load, inflammation and collection differ from healthy low-biomass brain; detection is not homeostasis." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 52, "pmid": "19335164", "title": "The expansion of the microbiological spectrum of brain abscesses with use of multiple 16S ribosomal DNA sequencing.", "citation": "Al Masalma M, Armougom F, Scheld WM et al. The expansion of the microbiological spectrum of brain abscesses with use of multiple 16S ribosomal DNA sequencing. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2009.", "doi": "10.1086/597578", "pmcid": "", "url": "https://pubmed.ncbi.nlm.nih.gov/19335164/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/19335164/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID19335164", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "human infection diagnostic comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Prospective 20-patient abscess comparison identifies 72 sequenced strains versus 22 culture strains and expands species spectrum.", "what_it_does_not_show": "Clinically localized infection establishes microbes can enter brain, without normal residence or neurodegenerative community causality.", "confounders_present": [ "Clinically localized infection establishes microbes can enter brain, without normal residence or neurodegenerative community causality." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 53, "pmid": "39509244", "title": "Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization.", "citation": "Mbongo W, Laga AC, Solomon IH et al. Detection of Gram-positive and Gram-negative bacteria in brain abscesses by 16S rRNA in situ hybridization. Journal of neuropathology and experimental neurology. 2025.", "doi": "10.1093/jnen/nlae118", "pmcid": "PMC11747221", "url": "https://pubmed.ncbi.nlm.nih.gov/39509244/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/39509244/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID39509244", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human infection diagnostic comparator", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "63 abscess cases yield 18 ISH positives; reported 35% sensitivity/93% specificity versus the composite comparator.", "what_it_does_not_show": "Negative ISH cannot exclude all infection, and abscess diagnostic performance cannot establish healthy-tissue assay sensitivity. Online 2024, issue 2025.", "confounders_present": [ "Negative ISH cannot exclude all infection, and abscess diagnostic performance cannot establish healthy-tissue assay sensitivity. Online 2024, issue 2025." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 54, "pmid": "18829386", "title": "Initial characterization of Chlamydophila (Chlamydia) pneumoniae cultured from the late-onset Alzheimer brain.", "citation": "Dreses-Werringloer U, Bhuiyan M, Zhao Y et al. Initial characterization of Chlamydophila (Chlamydia) pneumoniae cultured from the late-onset Alzheimer brain. International journal of medical microbiology : IJMM. 2009.", "doi": "10.1016/j.ijmm.2008.07.002", "pmcid": "PMC2730674", "url": "https://pubmed.ncbi.nlm.nih.gov/18829386/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/18829386/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID18829386", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Moderate", "system": "human AD autopsy culture", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Two AD brain-derived Chlamydia pneumoniae isolates were cultured through HEp-2 passages and characterized genetically.", "what_it_does_not_show": "A substantive viability positive in diseased autopsy tissue; does not establish community residence in living brains, healthy controls or AD necessity.", "confounders_present": [ "A substantive viability positive in diseased autopsy tissue; does not establish community residence in living brains, healthy controls or AD necessity." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 55, "pmid": "20863379", "title": "Immunohistological detection of Chlamydia pneumoniae in the Alzheimer's disease brain.", "citation": "Hammond CJ, Hallock LR, Howanski RJ et al. Immunohistological detection of Chlamydia pneumoniae in the Alzheimer's disease brain. BMC neuroscience. 2010.", "doi": "10.1186/1471-2202-11-121", "pmcid": "PMC2949767", "url": "https://pubmed.ncbi.nlm.nih.gov/20863379/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/20863379/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID20863379", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC2" ], "favors_models": [], "evidence_class": "Weak", "system": "human postmortem", "decisive_perturbation": false, "endogenous": false, "direction": "supports", "what_it_shows": "Five AD/five control immunohistological comparisons localize Chlamydia signals near, but not invariably within, amyloid deposits.", "what_it_does_not_show": "Proximity and antibody controls do not establish disease ordering, viable community or microbial causation.", "confounders_present": [ "Proximity and antibody controls do not establish disease ordering, viable community or microbial causation." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 56, "pmid": "30746447", "title": "Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors.", "citation": "Dominy SS, Lynch C, Ermini F et al. Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science advances. 2019.", "doi": "10.1126/sciadv.aau3333", "pmcid": "PMC6357742", "url": "https://pubmed.ncbi.nlm.nih.gov/30746447/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/30746447/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID30746447", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "human tissue and forced animal infection", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Human AD gingipain signals accompany inoculated-mouse bacterial load and small-molecule inhibition effects on neurodegenerative readouts.", "what_it_does_not_show": "Forced pathogen exposure and protease inhibition are not removal/rescue of an endogenous human resident community.", "confounders_present": [ "Forced pathogen exposure and protease inhibition are not removal/rescue of an endogenous human resident community." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 57, "pmid": "36631446", "title": "Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway.", "citation": "Lei S, Li J, Yu J et al. Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway. International journal of oral science. 2023.", "doi": "10.1038/s41368-022-00215-y", "pmcid": "PMC9834243", "url": "https://pubmed.ncbi.nlm.nih.gov/36631446/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/36631446/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID36631446", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC1", "SC3" ], "favors_models": [], "evidence_class": "Moderate", "system": "forced rat infection and culture", "decisive_perturbation": true, "endogenous": false, "direction": "supports", "what_it_shows": "Repeated intravenous P. gingivalis exposure changes BBB transcytosis; Cav/Mfsd-related interventions affect barrier readouts.", "what_it_does_not_show": "Installed bacteremia can permit entry; it cannot establish stable homeostatic human residence or sporadic-disease primacy.", "confounders_present": [ "Installed bacteremia can permit entry; it cannot establish stable homeostatic human residence or sporadic-disease primacy." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 58, "pmid": "32776951", "title": "Evidence for contamination as the origin for bacteria found in human placenta rather than a microbiota.", "citation": "Gschwind R, Fournier T, Kennedy S et al. Evidence for contamination as the origin for bacteria found in human placenta rather than a microbiota. PloS one. 2020.", "doi": "10.1371/journal.pone.0237232", "pmcid": "PMC7416914", "url": "https://pubmed.ncbi.nlm.nih.gov/32776951/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32776951/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID32776951", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "human placenta comparator", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "38-woman placenta culture/qPCR and selected sequencing distinguish surface organisms from internal signals matching blanks/database artifacts.", "what_it_does_not_show": "Sterile-tissue comparator highlights contamination control, but placenta absence does not prove adult brain absence.", "confounders_present": [ "Sterile-tissue comparator highlights contamination control, but placenta absence does not prove adult brain absence." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] }, { "n": 59, "pmid": "32376701", "title": "Lack of Evidence for Microbiota in the Placental and Fetal Tissues of Rhesus Macaques.", "citation": "Theis KR, Romero R, Winters AD et al. Lack of Evidence for Microbiota in the Placental and Fetal Tissues of Rhesus Macaques. mSphere. 2020.", "doi": "10.1128/mSphere.00210-20", "pmcid": "PMC7203455", "url": "https://pubmed.ncbi.nlm.nih.gov/32376701/", "source_pointer": "https://pubmed.ncbi.nlm.nih.gov/32376701/", "tier": "A", "source_tier": "A", "kind": "primary", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID32376701", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "relates_to_subclaims": [ "SC2" ], "favors_models": [], "evidence_class": "Strong", "system": "rhesus fetal tissue comparator", "decisive_perturbation": true, "endogenous": false, "direction": "contradicts", "what_it_shows": "Cesarean fetal brain/placenta signals do not exceed controls; isolated C. acnes also occurs in controls while positive controls work.", "what_it_does_not_show": "Restricted fetal macaque setting cannot settle adult human brain ecology; a valuable organ/method comparator only.", "confounders_present": [ "Restricted fetal macaque setting cannot settle adult human brain ecology; a valuable organ/method comparator only." ], "verification": "verified", "verification_note": "Bounded source attribution; not proof of the nominal mechanism.", "citation_context": { "retrieved": false, "supporting_count": 0, "mentioning_count": 0, "contrasting_count": 0, "notable_contrasting_statements": [] }, "shared_components": [] } ], "verification_summary": { "load_bearing_claims_checked": 63, "verified": 63, "unverified": 0, "contradicted": 0, "note": "Verified attribution is distinct from mechanism truth or complete body access." }, "factual_issues_found": [], "cap_rules_applied": [ { "subclaim_id": "SC1", "cap": "Α", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Use for ideas sustained mainly by contaminated signal, weak association, or conceptual enthusiasm.", "specific_trigger": "Α: orthogonal positive surgical/autopsy signals exist, but no independent viable strain-resolved living-human community replication excludes the demonstrated artifact alternatives. This is an unresolved existence gate, not a finding of universal sterility.", "resulting_ceiling": "Α" }, { "subclaim_id": "SC2", "cap": "Β", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Association-only microbiome work caps at Β.", "specific_trigger": "Β: controls and edge/core comparisons improve specificity, but no complete human case rules out reagent, host, vascular and preanalytic origins together; host-aware null and assay-recovery failures constrain both directions.", "resulting_ceiling": "Β" }, { "subclaim_id": "SC3", "cap": "Γ", "cap_source": "rubric", "triggered": true, "trigger_text_quoted": "Association plus mechanistic in vitro support, or host-pathway plausibility, caps at Γ.", "specific_trigger": "Γ: microbial products and installed infection can change relevant readouts, but resident-human community removal/rescue and neurodegenerative phenotype movement are absent from the examined corpus.", "resulting_ceiling": "Γ" } ], "cap_precedence_resolutions": [ { "collision": "Perturbation in a defined setting versus broader inference", "subclaim_scope_cap_binds_on": "The living human brain harbors a resident microbial community that contributes causally to neurodegeneration.", "subclaim_scope_threshold_binds_on": "The precise experimentally tested subclaim scope", "resolution": "The 04 low-biomass Α existence gate governs SC1. Forced transfer can cross Δ only for a demonstrated recipient phenotype; the 2013 transfer had no neurological disease phenotype and different donors in its heat contrast. Salmon culture supports its own restricted ecological model but cannot lift living-human residence. Convergent human positives are assessed together; their shared unexcluded viability/preanalytic failure modes still leave the gate unresolved.", "note": "Convergent lines are assessed as a set; one weak leg is not re-capped over the assembled case." } ], "boundary_check_BGD": [ { "subclaim_id": "SC1", "field_valid_perturbation_quote": "\n- Gnotobiotic or transfer experiment showing phenotype movement, at minimum\n- Even without defined-consortium precision or robust rescue, a transfer paradigm in vivo is the minimum that crosses this threshold\n\nPer **Cap precedence** above, a gnotobiotic or forced-transfer experiment crosses Δ for the recipient-animal subclaim it was actually run in, while universal cap 5 (seeding or forced-transfer paradigms cap at Γ) still blocks the inference from that result to endogenous human biology — score the two scopes separately rather than choosing between the rules.", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "PMID23355888, PMID33771222, PMID40284643, PMID29232157, PMID39292785, PMID34908504, PMID32310171, PMID36202168, PMID32244052, PMID37741170, PMID19335164, PMID39509244, PMID18829386, PMID30746447, PMID36631446", "gamma_hard_rules_triggered": [ "No endogenous human resident-community strain subtraction/addition with disease phenotype has been established.", "Forced human-homogenate or pathogen transfer is bounded to the recipient system; antigen, DNA and RNA signals do not alone establish viability." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Α: orthogonal positive surgical/autopsy signals exist, but no independent viable strain-resolved living-human community replication excludes the demonstrated artifact alternatives. This is an unresolved existence gate, not a finding of universal sterility.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC2", "field_valid_perturbation_quote": "\n- Gnotobiotic or transfer experiment showing phenotype movement, at minimum\n- Even without defined-consortium precision or robust rescue, a transfer paradigm in vivo is the minimum that crosses this threshold\n\nPer **Cap precedence** above, a gnotobiotic or forced-transfer experiment crosses Δ for the recipient-animal subclaim it was actually run in, while universal cap 5 (seeding or forced-transfer paradigms cap at Γ) still blocks the inference from that result to endogenous human biology — score the two scopes separately rather than choosing between the rules.", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "PMID23355888, PMID33771222, PMID40284643, PMID29232157, PMID39292785, PMID34908504, PMID32310171, PMID25387460, PMID30887686, PMID32046792, PMID31412780, PMID34162397, PMID32518181, PMID34834931, PMID37784008, PMID33382980, PMID25944184, PMID36357382, PMID32828122, PMID30558668, PMID31164452, PMID27107811, PMID38145697, PMID27688978, PMID31239396, PMID34101489, PMID30801029, PMID30383890, PMID32244052, PMID37741170, PMID19335164, PMID39509244, PMID18829386, PMID32776951, PMID32376701", "gamma_hard_rules_triggered": [ "No endogenous human resident-community strain subtraction/addition with disease phenotype has been established.", "Forced human-homogenate or pathogen transfer is bounded to the recipient system; antigen, DNA and RNA signals do not alone establish viability." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Β: controls and edge/core comparisons improve specificity, but no complete human case rules out reagent, host, vascular and preanalytic origins together; host-aware null and assay-recovery failures constrain both directions.", "ceiling_from_boundary_check": "Γ" }, { "subclaim_id": "SC3", "field_valid_perturbation_quote": "\n- Gnotobiotic or transfer experiment showing phenotype movement, at minimum\n- Even without defined-consortium precision or robust rescue, a transfer paradigm in vivo is the minimum that crosses this threshold\n\nPer **Cap precedence** above, a gnotobiotic or forced-transfer experiment crosses Δ for the recipient-animal subclaim it was actually run in, while universal cap 5 (seeding or forced-transfer paradigms cap at Γ) still blocks the inference from that result to endogenous human biology — score the two scopes separately rather than choosing between the rules.", "qualifying_evidence_present": "no", "qualifying_evidence_citation": "PMID23355888, PMID29232157, PMID39292785, PMID36202168, PMID30746447, PMID36631446", "gamma_hard_rules_triggered": [ "No endogenous human resident-community strain subtraction/addition with disease phenotype has been established.", "Forced human-homogenate or pathogen transfer is bounded to the recipient system; antigen, DNA and RNA signals do not alone establish viability." ], "disease_phenotype_relevance": "yes", "perturbation_result_positive": "no", "perturbation_result_note": "Γ: microbial products and installed infection can change relevant readouts, but resident-human community removal/rescue and neurodegenerative phenotype movement are absent from the examined corpus.", "ceiling_from_boundary_check": "Γ" } ], "thresholds_tested": [ { "subclaim_id": "SC1", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "no", "supporting_evidence": [ "[1] Surgical epilepsy and autopsy brain show bacterial RNA, glial antigen/ISH and seven-week RNA recovery after implantation in Rag1-null mice, with PCR water and tool controls.", "[2] 47 postmortem and three surgical samples were analyzed with extraction/PCR blanks, mock dilutions, qPCR and host alignment; disease-differentiating taxa were host off-targets.", "[5] 86 samples from 31 specimens, 14 AD/17 controls, with four extraction blanks and edge/core sampling; no edge enrichment and some disease-associated taxa after decontamination.", "[22] Sepsis mice have viable brain bacteria around day five but not day 14; human postmortem sepsis brain signals correlate with the systemic source.", "[23] Perfused trout brains show RNA/DNA, localized bacteria and 54 cultured isolates; buffer/CSF negatives, environment controls, antibiotics and tagged strain colonization corroborate fish residence.", "[24] 23 healthy pregnant women, 116 CSF/control samples and paired metatranscriptomics show no active viable microbial community after contamination correction.", "[27] Two AD cohorts show processing/postmortem effects greater than the limited AD-control differences.", "[28] 22 HIV/11 control human and 11 SIV/4 control primate specimens show microbial molecules; peptidoglycan alters CCR5/HIV and neuronal mitochondrial readouts.", "[50] 79 samples from 54 patients include 51 intracranial abscesses, with sequencing detecting broader polymicrobial pathogens.", "[51] Nanopore 16S of 27 abscess pus samples detects more anaerobic/polymicrobial findings than culture.", "[52] Prospective 20-patient abscess comparison identifies 72 sequenced strains versus 22 culture strains and expands species spectrum.", "[53] 63 abscess cases yield 18 ISH positives; reported 35% sensitivity/93% specificity versus the composite comparator.", "[54] Two AD brain-derived Chlamydia pneumoniae isolates were cultured through HEp-2 passages and characterized genetically.", "[56] Human AD gingipain signals accompany inoculated-mouse bacterial load and small-molecule inhibition effects on neurodegenerative readouts.", "[57] Repeated intravenous P. gingivalis exposure changes BBB transcytosis; Cav/Mfsd-related interventions affect barrier readouts." ], "what_would_cross_it": "A prespecified causal test matching this subclaim, with mechanistic engagement, meaningful phenotype change and an appropriate negative control." }, { "subclaim_id": "SC2", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "no", "supporting_evidence": [ "[1] Surgical epilepsy and autopsy brain show bacterial RNA, glial antigen/ISH and seven-week RNA recovery after implantation in Rag1-null mice, with PCR water and tool controls.", "[2] 47 postmortem and three surgical samples were analyzed with extraction/PCR blanks, mock dilutions, qPCR and host alignment; disease-differentiating taxa were host off-targets.", "[5] 86 samples from 31 specimens, 14 AD/17 controls, with four extraction blanks and edge/core sampling; no edge enrichment and some disease-associated taxa after decontamination.", "[22] Sepsis mice have viable brain bacteria around day five but not day 14; human postmortem sepsis brain signals correlate with the systemic source.", "[23] Perfused trout brains show RNA/DNA, localized bacteria and 54 cultured isolates; buffer/CSF negatives, environment controls, antibiotics and tagged strain colonization corroborate fish residence.", "[24] 23 healthy pregnant women, 116 CSF/control samples and paired metatranscriptomics show no active viable microbial community after contamination correction.", "[27] Two AD cohorts show processing/postmortem effects greater than the limited AD-control differences.", "[29] Serial pure-culture dilutions across three facilities and multiple kits produce kit-specific false profiles; cohort-age clustering tracked kit batches.", "[30] 144 negative controls over five years show kit/laboratory/researcher/month variation in contaminant communities.", "[31] Low-biomass metagenomic decontamination uses coverage and batch variation and is tested in clinical cfDNA settings.", "[32] 23-subject airway study attributes substantial low-biomass profiles to laboratory contamination.", "[33] A contaminant-controlled workflow detects microbial cfDNA exceeding blanks in plasma samples.", "[34] Mock serial dilutions and clinical respiratory samples reveal stochastic profiles below the tested bacterial-load range.", "[35] Seven blank libraries contain 14 viral contaminants, demonstrating reagent-derived RNA/viral reads.", "[36] Synthetic/public benchmarks assess host-removal accuracy; long-read performance remains incomplete.", "[37] Pan-cancer profiles use center/batch and matched tissue information to distinguish candidate tissue signals from contaminants.", "[38] CS-SCORE benchmarks human-read removal with computational efficiency benefits.", "[39] Squeegee cross-sample contaminant identification is benchmarked against control-based approaches.", "[40] Defined mammalian/bacterial FFPE blocks compare recovery with qPCR, 16S and whole-genome methods.", "[41] decontam uses frequency/prevalence with culture dilution and biological cohorts to identify contaminants.", "[42] Known mock dilutions quantify contamination and false deletion; blank-only filtering removes 20.1–33.9% of true ASVs and misses many contaminants.", "[43] qPCR bacterial-load-aware removal preserves known culture members and reduces tested contaminants.", "[44] Alternative two-stage 16S/ITS amplification improves low-biomass sequencing in mocks and clinical samples.", "[45] 54-species mock and environmental microsamples validate very-low-input shotgun libraries with explicit complexity/contamination limits.", "[46] Unique bacterial assignments across two laboratories reveal well-to-well contamination, strongest at low biomass.", "[47] Mock and bile analyses with repeated controls show stochastic amplification and incomplete single-blank coverage.", "[48] Six inference approaches across biomass dilutions compare false sequence/OTU calls; ASV methods improve precision.", "[49] DNase treatment of PCR master mixes reduces measured reagent contamination about 99% in the tested protocol.", "[50] 79 samples from 54 patients include 51 intracranial abscesses, with sequencing detecting broader polymicrobial pathogens.", "[51] Nanopore 16S of 27 abscess pus samples detects more anaerobic/polymicrobial findings than culture.", "[52] Prospective 20-patient abscess comparison identifies 72 sequenced strains versus 22 culture strains and expands species spectrum.", "[53] 63 abscess cases yield 18 ISH positives; reported 35% sensitivity/93% specificity versus the composite comparator.", "[54] Two AD brain-derived Chlamydia pneumoniae isolates were cultured through HEp-2 passages and characterized genetically.", "[58] 38-woman placenta culture/qPCR and selected sequencing distinguish surface organisms from internal signals matching blanks/database artifacts.", "[59] Cesarean fetal brain/placenta signals do not exceed controls; isolated C. acnes also occurs in controls while positive controls work." ], "what_would_cross_it": "A prespecified causal test matching this subclaim, with mechanistic engagement, meaningful phenotype change and an appropriate negative control." }, { "subclaim_id": "SC3", "threshold": "Δ", "requirement_quoted": "Requires a transfer paradigm or causal perturbation in vivo.", "satisfied": "no", "supporting_evidence": [ "[1] Surgical epilepsy and autopsy brain show bacterial RNA, glial antigen/ISH and seven-week RNA recovery after implantation in Rag1-null mice, with PCR water and tool controls.", "[22] Sepsis mice have viable brain bacteria around day five but not day 14; human postmortem sepsis brain signals correlate with the systemic source.", "[23] Perfused trout brains show RNA/DNA, localized bacteria and 54 cultured isolates; buffer/CSF negatives, environment controls, antibiotics and tagged strain colonization corroborate fish residence.", "[28] 22 HIV/11 control human and 11 SIV/4 control primate specimens show microbial molecules; peptidoglycan alters CCR5/HIV and neuronal mitochondrial readouts.", "[56] Human AD gingipain signals accompany inoculated-mouse bacterial load and small-molecule inhibition effects on neurodegenerative readouts.", "[57] Repeated intravenous P. gingivalis exposure changes BBB transcytosis; Cav/Mfsd-related interventions affect barrier readouts." ], "what_would_cross_it": "A prespecified causal test matching this subclaim, with mechanistic engagement, meaningful phenotype change and an appropriate negative control." } ], "generalization_check": { "generalization_tested": "yes", "context_boundary_mapped": "yes", "internal_negative_controls": [ "2013 water/tool controls, scrambled ISH probes and SPF animal comparators; transfer heat/donor confounding retained.", "2021 extraction, library/PCR, water/buffer negatives, diluted mock communities and host genome alignment; positive-control lysis failures retained.", "2025 edge/core samples, four extraction blanks and alternative zero filtering; nonsignificance not treated as equivalence.", "2024 trout perfusion, same-animal CSF, buffer plates and nonmatching environmental isolates; independent human replication remains missing." ], "note": "Explicit comparisons: epilepsy surgery versus autopsy, AD versus PD/HIV/sepsis, CSF versus parenchyma, adult human versus fetal macaque/teleost, molecular products versus cultured organisms. No specimen- or responder-defined rescue of the registered scope." }, "falsification_patterns_met": [ { "pattern": "Host-aware analysis removes apparent PD-specific bacterial differences", "evidence": "PMID33771222 manual alignment identifies disease-differentiating taxa as human off-targets.", "downgrade_applied": false } ], "pitfalls_flagged": [ { "pitfall": "RNA or antigens equated with viability", "where": "Human molecular positives versus culture; reagent RNA is possible." }, { "pitfall": "Absent provider excerpt treated as absent study control", "where": "Alonso 2018 documents multiple PCR negatives, though sequenced bacterial extraction blanks remain unverified." }, { "pitfall": "Nonsignificance treated as equivalence", "where": "2025 edge/core posterior intervals include zero but do not set an equivalence margin." }, { "pitfall": "Inferred LDA order treated as prospective disease time", "where": "2023 source explicitly uses a health-before-disease ordering assumption." }, { "pitfall": "Fish, infection and fluid results transferred to living human parenchyma", "where": "Scope boundaries in SC1/SC3." } ], "causal_tally_audit": { "tally_claimed_by_document": 38, "tally_after_audit": 38, "items_rejected": [ "Null and negative contrasts are discriminators, not positive threshold crossings. Reports and replications are not independent causal lines.", "Shared cohorts, experimental platforms, transgenic lineages and repeated outcomes do not constitute fully independent causal lines." ] }, "steelman": { "case_one_rung_higher": "Steelman Β: independent molecular methods, surgical samples, rapid autopsy and cultured AD isolates support some genuine microbial material and occasional organisms. This justifies investigation, but does not establish the stable living-human community required by SC1.", "case_one_rung_lower": "There is no rung below Α. An assertion of refuted or universally sterile would overread the assay-specific null, culture positives and strong fish evidence.", "which_rejected": "Keep Α as insufficient establishment of the registered existence gate, without converting it into universal absence; retain narrow positive findings and higher restricted-model scores.", "blocking_cap_threshold_or_missing_experiment": "Missing experiment: A prospectively registered multi-laboratory living-tissue study coupling quantitative strain-resolved genomes/RNA, recoverable viability and in situ localization to matched controls, followed by selective removal/reconstitution in a biologically matched model only after existence is demonstrated." }, "final_score": { "hsef_level": "Α", "hsef_descriptor": "Speculative / narrative", "confidence": "Moderate", "confidence_rationale": "Fifty-nine primary reports across many laboratories, assay modalities and organ comparators, but the band is held at Moderate by substantive evidence-quality concerns the review documents: the artifact mechanisms are themselves experimentally demonstrated (kit dilution series, well-to-well cross-talk, host mispriming), no human study yet excludes reagent, host, vascular and preanalytic origins together, the host-aware null is bounded by its own positive-control recovery failures, multiple samples per donor are not independent participants, and the strongest positive residency evidence sits in a single teleost investigative platform. Confidence reflects evidence density and reproducibility, not reviewer access depth or correctness.", "rests_on_non_peer_reviewed_work": false, "rationale": "Preregistered primary-subclaim aggregation returns Α because SC1 living-human community existence remains unresolved under the low-biomass contamination gate. SC2 Β and SC3 Γ do not replace that prerequisite. Weakest-link and scope-matched sensitivities also return Α. Positive fish ecology and AD autopsy culture are explicitly retained rather than dismissed." }, "role_of_mechanism": { "classification": "epiphenomenon", "derivation_step_matched": 2, "derivation": "Canonical step 2 applies: no causal dependency in either direction is demonstrated for the nominal resident-human community. This label records co-occurrence without demonstrated dependency, not proof of biological inertness. Product ingress and installed infection can have causal effects in separate settings.", "tournament_used_as_tiebreaker": false, "note": "Derived from causal direction, not tournament rank." }, "extended_scoring_MSD": { "momentum": { "value": "Mechanistic only", "artifact": "Active mechanistic and methodological work only. The named artifacts — 2023 full-length profiling, 2024 salmon culture and 2025 human edge/core sampling — are completed publications, and the review itself states that no current recruiting trial is asserted; a completed report is not an experiment being run that could cross the next threshold. No ongoing multi-laboratory living-human viability study addressing the SC1 existence gate was identified.", "justification": "Active mechanistic and methodological work only. The named artifacts — 2023 full-length profiling, 2024 salmon culture and 2025 human edge/core sampling — are completed publications, and the review itself states that no current recruiting trial is asserted; a completed report is not an experiment being run that could cross the next threshold. No ongoing multi-laboratory living-human viability study addressing the SC1 existence gate was identified." }, "stability": { "value": "Stable", "trigger": "No named pending result is asserted to be likely to move the registered score imminently.", "justification": "No named pending result is asserted to be likely to move the registered score imminently." }, "divergence": { "implied_level": null, "implied_level_basis": "No single field-implied level is defensible from conflicting framings.", "assessed_level": "Α", "gap_in_rungs": null, "value": "Contested", "justification": "No manufactured field consensus or arithmetic gap." }, "calibration_note": "M/S/D never modify HSEF level or confidence." }, "change_record": { "applies": false, "prior_level": "Ranking categorical verdict visible; no prior letter used as a target", "prior_confidence": null, "prior_source": null, "derived_before_consulting_prior": false, "new_level": "Α", "direction": "newly assigned", "what_moved_it": "Fresh primary evidence appraisal; not blinded.", "divergence_from_other_reviewers": null }, "proposed_decisive_experiments": [ { "name": "Registered boundary experiment", "experiment": "A prospectively registered multi-laboratory living-tissue study coupling quantitative strain-resolved genomes/RNA, recoverable viability and in situ localization to matched controls, followed by selective removal/reconstitution in a biologically matched model only after existence is demonstrated.", "readout": "Absolute organism recovery above validated protocol background, viable strain concordance, vascular exclusion and separate neuronal/functional endpoints", "critical_control": "Independent collection/tool/reagent/PCR blanks, host-aware mapping, blind spike-ins with difficult-to-lyse taxa, matched culture controls and same-donor heat comparisons", "supporting_result": "The same viable localized strains reproducibly exceed controls across laboratories and selective removal/rescue moves neurodegenerative phenotype", "falsifying_result": "Signal follows lots, host sequences, blood or collection delay, or confirmed removal leaves disease intact" } ], "knowledge_gaps": [ { "name": "Gap 1", "statement": "Independent quantitative viable-community replication in promptly collected living human parenchyma is missing.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 2", "statement": "Vascular content, peripheral products and tissue localization must be distinguished by strain-matched orthogonal assays.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 3", "statement": "Protocol-specific detection/recovery limits must include hard-to-lyse organisms; the 2021 positive-control misses matter.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 4", "statement": "Use same-donor aliquots for heated/unheated transfer; the 2013 donor contrast cannot isolate viability.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 5", "statement": "Separate RNA contamination, dormant/unculturable possibilities and recoverable viability without defining residence solely from whichever assay is positive.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 6", "statement": "Cross-sectional microbial class ordering needs longitudinal or intervention confirmation; no inferred timeline should be presented as observed disease progression.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 7", "statement": "A resident-community disease experiment requires selective subtraction/addition with strain engagement and meaningful neuronal endpoints, distinct from forced infection.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 8", "statement": "Fish persistence beyond 14 days and its functional consequences remain open, with no direct human extrapolation.", "relevance": "Limits mechanism identification or scope." }, { "name": "Gap 9", "statement": "Edge/core nonsignificance needs predefined equivalence margins, absolute quantification and independent collection controls.", "relevance": "Limits mechanism identification or scope." } ], "review_metadata": { "review_date": "2026-10-08", "reviewer": "Codex", "evidence_base_note": "59 primary reports; literature cutoff 2026-10-08; source examination UTC date 2026-10-08; bounded critical review, not exhaustive systematic review.", "literature_tools_available": true, "literature_tools_note": "Life Sciences Literature PubMed/Entrez; attempted Europe PMC XML and successful public NCBI PMC direct HTTPS access are separately logged. Signed-in Consensus browser discovery and targeted indexed full-text checks are reconciled with original sections; failed matches and source substitutions remain explicit. Zero Consensus API calls. SciSpace discovery was also used; matched primary leads were resolved to original records before counting. See scispace-leads.json.", "skill_version": "5.3", "validator_run": "exact archived v5.3 validator 2.3; see validator.txt", "validator_warnings_addressed": "Phenomenon entry was restated as the preregistered causal claim. No real phenomenon is labelled refuted; warning is explicitly justified.", "consensus_consistency_audit": "2026-10-09; supplementary provenance/source reconciliation; original grading retained; prior grades visible." }, "is_calibration_entry": { "value": false, "entry_role": "not_calibration", "blind_graded": null, "completed_blinded_calibration": false, "expected_band_sealed_at": "", "target_sha256": "", "target_authorship": "not applicable", "target_author_saw_review": null, "future_run_status": "not prepared", "unblinded_reason": "Ranking categorical verdict and index guidance were visible. No completed blinded calibration claimed." }, "upper_ladder_check": { "final_level_below_zeta": true, "equivalents_considered": [ { "kind": "mendelian_randomization", "available": false, "why_not_sufficient": "Strain-resolved living-human colonization, selective removal/rescue, dose-response and eradication natural experiments are live upper-ladder routes. None in the examined corpus establishes the entire resident-human community claim; ethical limits on healthy sampling do not constitute disproof." }, { "kind": "natural_experiment", "available": false, "why_not_sufficient": "Strain-resolved living-human colonization, selective removal/rescue, dose-response and eradication natural experiments are live upper-ladder routes. None in the examined corpus establishes the entire resident-human community claim; ethical limits on healthy sampling do not constitute disproof." }, { "kind": "dose_response_across_populations", "available": false, "why_not_sufficient": "Strain-resolved living-human colonization, selective removal/rescue, dose-response and eradication natural experiments are live upper-ladder routes. None in the examined corpus establishes the entire resident-human community claim; ethical limits on healthy sampling do not constitute disproof." }, { "kind": "withdrawal_rechallenge", "available": false, "why_not_sufficient": "Strain-resolved living-human colonization, selective removal/rescue, dose-response and eradication natural experiments are live upper-ladder routes. None in the examined corpus establishes the entire resident-human community claim; ethical limits on healthy sampling do not constitute disproof." }, { "kind": "therapeutic_perturbation_hard_endpoint", "available": false, "why_not_sufficient": "Strain-resolved living-human colonization, selective removal/rescue, dose-response and eradication natural experiments are live upper-ladder routes. None in the examined corpus establishes the entire resident-human community claim; ethical limits on healthy sampling do not constitute disproof." } ], "convergence_present": true, "cap_reapplied_to_convergent_set": false }, "provenance_header": { "sources_total": 59, "claims_total": 63, "claims_verified": 63, "claims_unverified": 0, "claims_contradicted": 0, "tier_a_sources": 59, "generated_by": "Codex; HSEF v5.3", "gate_passed": true }, "claims": [ { "id": "C1", "text": "Surgical epilepsy and autopsy brain show bacterial RNA, glial antigen/ISH and seven-week RNA recovery after implantation in Rag1-null mice, with PCR water and tool controls. No human culture or resident-community disease phenotype; heated ODC13 and unheated ODC14 are different donors, confounding the viability contrast. SURG is epilepsy tissue, not healthy population sampling.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 1 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph15, 1:Results:paragraph17, 1:Results:paragraph18, 1:Results:paragraph19, 1:Results:paragraph23, 1:Results:paragraph24, 3:Materials and Methods:paragraph4, 3:Materials and Methods:paragraph5, 3:Materials and Methods:paragraph10. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C2", "text": "47 postmortem and three surgical samples were analyzed with extraction/PCR blanks, mock dilutions, qPCR and host alignment; disease-differentiating taxa were host off-targets. Null is bounded to this assay/cohort. Positive mock missed Listeria and under-recovered Bacillus without mechanical lysis; residual human bacterial load was not literally zero.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 2 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph15, 1:Methods:paragraph23, 1:Methods:paragraph26, 1:Methods:paragraph28, 2:Results:paragraph2, 2:Results:paragraph15, 2:Results:paragraph16, 2:Results:paragraph18, 2:Results:paragraph20, 2:Results:paragraph24, 2:Results:paragraph27, 2:Results:paragraph31. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C3", "text": "AD temporal tissue yields more normalized 16S reads than controls; original Discussion acknowledges human 18S coamplification and possible secondary infection. Normalized library read counts do not quantify absolute organisms or viability; age/postmortem matching cannot alone exclude reagent or host artifacts.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 3 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and Methods:paragraph0, 1:Materials and Methods:paragraph5, 1:Materials and Methods:paragraph6, 1:Materials and Methods:paragraph7, 1:Materials and Methods:paragraph11, 3:Discussion:paragraph0, 3:Discussion:paragraph2, 3:Discussion:paragraph3, 3:Discussion:paragraph9. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C4", "text": "High-resolution 16S profiling reports bacterial differences across AD/PD-associated brain regions and peripheral comparator tissues. Taxonomic detection cannot establish living parenchymal residence, temporal direction or causal disease contribution; abstract-only controls.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 4 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C5", "text": "86 samples from 31 specimens, 14 AD/17 controls, with four extraction blanks and edge/core sampling; no edge enrichment and some disease-associated taxa after decontamination. No edge enrichment is not statistical equivalence or absence of all contamination; both edge and core may share reagent/intravascular sources. No culture or prospective disease ordering.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 5 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:2. Materials and Methods:paragraph0, 1:2. Materials and Methods:paragraph4, 1:2. Materials and Methods:paragraph5, 1:2. Materials and Methods:paragraph6, 2:3. Results and Discussion:paragraph0, 2:3. Results and Discussion:paragraph3, 2:3. Results and Discussion:paragraph4, 2:3. Results and Discussion:paragraph6, 2:3. Results and Discussion:paragraph8. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C6", "text": "130 samples from 32 subjects and four extraction blanks support full-length 16S patterns; LDA extracts co-occurrence classes. LDA classes are not organism abundance or measured longitudinal time. Ordering assumes health precedes disease; inferred stages do not establish microbial initiation.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 6 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and methods:paragraph0, 1:Materials and methods:paragraph25, 1:Materials and methods:paragraph44, 1:Materials and methods:paragraph49. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C7", "text": "Bacterial products and microbial profiles vary by region in AD/control tissue, including widespread LPS immunoreactivity. LPS indicates material, not viability, and region differences permit entry/clearance or handling explanations; original body not examined.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 7 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C8", "text": "Seven Huntington disease brains show fungal/bacterial structures and sequence signals across regions. Same laboratory platforms recur; no contamination-resistant independent living-human community replication or causal intervention.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 8 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C9", "text": "Ten AD brains show fungal-antibody immunoreactivity in different regions alongside sequence-based evidence. Antibody structures and postmortem fungal DNA do not identify a reproducible viable community in living healthy brains.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 9 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C10", "text": "Fungal ITS sequencing in nine AD subjects identifies diverse species and regional differences. Amplified low-biomass taxonomic signals require matched blanks and viability; relative diversity does not establish causality.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 10 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C11", "text": "AD tissue shows polymicrobial antibody/PCR signals; Borrelia/chlamydial antibodies cross-react and targeted Borrelia/HSV PCR is negative in the tested series. Cross-reactive immunoreactivity cannot identify those pathogens; positive broad taxonomies and negative specific PCR test different targets.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 11 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C12", "text": "Six PD subjects show fungal and bacterial signals by immunohistology and sequencing. Small postmortem series from recurring platform, without prospective viability or removal/rescue; disease-associated entry remains possible.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 12 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C13", "text": "Corpora amylacea from several neurodegenerative diseases stain with antifungal antibodies. Storage/clearance bodies and antigens do not demonstrate live microbes or disease-specific causal residence.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 13 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C14", "text": "ALS CSF and brain contain fungal protein/DNA signals in reported assays. CSF and postmortem products are not living parenchymal community evidence; no phenotype-specific eradication.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 14 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C15", "text": "Intracellular fungal-like staining occurs in AD neurons, compared with experimentally Candida-infected animals. Infected-animal morphology supports assay plausibility but cannot identify viable human species or distinguish nonspecific staining.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 15 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C16", "text": "Fungal enolase, tubulin and chitin antibody signals appear in AD tissue, with some control positives and chitin-negative corpora amylacea. Multiple antigens are not culture or a strain-resolved community; heterogeneous negative/positive structures limit specificity.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 16 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C17", "text": "Fungal/bacterial profiling reports AD-control differences; original Methods describe rapid autopsy, sterile sampling and multiple PCR negatives. Negatives are documented, contrary to a blanket absent-controls claim. Methods examined do not establish independent sequenced bacterial extraction blanks, quantitative load, host screening or viability.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 17 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and Methods:paragraph1, 1:Materials and Methods:paragraph4, 1:Materials and Methods:paragraph5, 1:Materials and Methods:paragraph8, 1:Materials and Methods:paragraph9. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C18", "text": "Two AD corpora-amylacea preparations contain reported microbial and host proteins, with DNA assays supporting fungal signals. Protein attribution in small selected preparations does not establish living microbial residence or its necessity for disease.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 18 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C19", "text": "AD CSF slot-blot/PCR assays report fungal material. Fluid material need not reflect a viable parenchymal community; assay contamination and specificity need original control scrutiny.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 19 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C20", "text": "AD specimens show fungal protein/PCR signals interpreted as infection. Molecules can persist after clearance or enter from elsewhere; infection is distinct from a stable resident community.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 20 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C21", "text": "24 AD and 18 control brains contain LPS/E. coli K99 immunoreactivity, with stronger signals associated with AD pathology. Control positivity and pathology correlation do not establish viable bacteria, causal direction or resident-community necessity.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 21 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C22", "text": "Sepsis mice have viable brain bacteria around day five but not day 14; human postmortem sepsis brain signals correlate with the systemic source. Demonstrates transient disease-associated dissemination, not homeostatic residency or sporadic neurodegenerative causality.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 22 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C23", "text": "Perfused trout brains show RNA/DNA, localized bacteria and 54 cultured isolates; buffer/CSF negatives, environment controls, antibiotics and tagged strain colonization corroborate fish residence. Not human evidence. Tagged-strain persistence declines by day 14, brain isolates come from two fish for genome comparisons, and adult salmon LPS/amyloid association is not a causal degeneration intervention.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2", "SC3" ], "source_ns": [ 23 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph0, 1:RESULTS:paragraph2, 1:RESULTS:paragraph3, 1:RESULTS:paragraph10, 1:RESULTS:paragraph15, 1:RESULTS:paragraph16, 1:RESULTS:paragraph24. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C24", "text": "23 healthy pregnant women, 116 CSF/control samples and paired metatranscriptomics show no active viable microbial community after contamination correction. CSF is a distinct compartment and pregnancy a restricted population; cannot prove universal absence of parenchymal organisms.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 24 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C25", "text": "Four cadavers show tissue-specific postmortem microbial profiles and extraction-related differences. Postmortem presence cannot be back-extrapolated to living residence; tiny comparator does not explain every brain signal.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 25 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C26", "text": "40 cadavers sampled over 24–432 hours show organ- and postmortem-interval-associated communities. Long-delay autopsy dynamics do not imply all rapid-autopsy or surgical positives are postmortem invasion.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 26 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C27", "text": "Two AD cohorts show processing/postmortem effects greater than the limited AD-control differences. DNA may still be present; the null concerns disease signatures and study bias, not an absolute sterility proof.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 27 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C28", "text": "22 HIV/11 control human and 11 SIV/4 control primate specimens show microbial molecules; peptidoglycan alters CCR5/HIV and neuronal mitochondrial readouts. Translocated microbial molecules can act without resident viable bacteria; HIV-linked immune/barrier pathology is not sporadic neurodegeneration. Online 2022, issue 2023.", "carries_number": true, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 28 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C29", "text": "Serial pure-culture dilutions across three facilities and multiple kits produce kit-specific false profiles; cohort-age clustering tracked kit batches. Demonstrates a causal artifact mechanism, not proof that every positive human brain signal is contaminated; tested quantitative floors are protocol-specific.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 29 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph0, 1:Results:paragraph4, 1:Results:paragraph8, 1:Results:paragraph9, 1:Results:paragraph10, 1:Results:paragraph11, 1:Results:paragraph13. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C30", "text": "144 negative controls over five years show kit/laboratory/researcher/month variation in contaminant communities. A historical contaminant list cannot classify every future tissue taxon; this is methods evidence, not direct human-brain absence.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 30 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C31", "text": "Low-biomass metagenomic decontamination uses coverage and batch variation and is tested in clinical cfDNA settings. Algorithmic benchmarking in urine/amniotic settings does not measure brain viability or guarantee filtering accuracy there.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 31 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C32", "text": "23-subject airway study attributes substantial low-biomass profiles to laboratory contamination. Airway-specific fractions do not estimate the brain fraction; matched brain recovery controls remain necessary.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 32 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C33", "text": "A contaminant-controlled workflow detects microbial cfDNA exceeding blanks in plasma samples. Circulating DNA can exist without live resident plasma organisms and may contribute to brain tissue signals.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 33 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C34", "text": "Mock serial dilutions and clinical respiratory samples reveal stochastic profiles below the tested bacterial-load range. The numerical copy threshold is assay-specific and cannot be imposed as a universal brain cutoff.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 34 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C35", "text": "Seven blank libraries contain 14 viral contaminants, demonstrating reagent-derived RNA/viral reads. RNA detection alone cannot establish viability, but contamination in these reagents is not a universal explanation of all viral tissue findings.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 35 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C36", "text": "Synthetic/public benchmarks assess host-removal accuracy; long-read performance remains incomplete. A host-removal tool is not direct biological evidence for or against brain residence.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 36 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C37", "text": "Pan-cancer profiles use center/batch and matched tissue information to distinguish candidate tissue signals from contaminants. Cancer/mucosal tissue validation does not establish brain microbiota or living strain identity.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 37 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C38", "text": "CS-SCORE benchmarks human-read removal with computational efficiency benefits. Speed and genome filtering do not certify low-copy bacterial identification, tissue localization or viability.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 38 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C39", "text": "Squeegee cross-sample contaminant identification is benchmarked against control-based approaches. Data-driven decontamination does not replace independent physical blanks or prove brain community existence.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 39 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C40", "text": "Defined mammalian/bacterial FFPE blocks compare recovery with qPCR, 16S and whole-genome methods. Useful assay recovery standard; fixed mock blocks are not viable organisms in human brain.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 40 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C41", "text": "decontam uses frequency/prevalence with culture dilution and biological cohorts to identify contaminants. Model assumptions can fail with cross-contamination or shared true/background taxa; filtered signal is not automatically true residence.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 41 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C42", "text": "Known mock dilutions quantify contamination and false deletion; blank-only filtering removes 20.1–33.9% of true ASVs and misses many contaminants. No algorithm is perfect across mixtures. Unknown-source SourceTracker fails substantially, while known-source success cannot be assumed for brain.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 42 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:RESULTS:paragraph12, 1:RESULTS:paragraph17, 1:RESULTS:paragraph18, 1:RESULTS:paragraph20, 1:RESULTS:paragraph22, 1:RESULTS:paragraph25. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C43", "text": "qPCR bacterial-load-aware removal preserves known culture members and reduces tested contaminants. Some sample cross-contaminants escape blank-based correction; recovery must be tested for the actual brain protocol.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 43 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C44", "text": "Alternative two-stage 16S/ITS amplification improves low-biomass sequencing in mocks and clinical samples. Amplification yield or consistency cannot demonstrate microbial viability or absence of stochastic errors below recovery limits.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 44 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C45", "text": "54-species mock and environmental microsamples validate very-low-input shotgun libraries with explicit complexity/contamination limits. Real microspatial variation is possible; low-input validation in known communities is not automatic brain validity.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 45 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C46", "text": "Unique bacterial assignments across two laboratories reveal well-to-well contamination, strongest at low biomass. Cross-contamination can introduce real tissue taxa into blanks; blanket deletion of blank taxa can therefore erase true organisms.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 46 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C47", "text": "Mock and bile analyses with repeated controls show stochastic amplification and incomplete single-blank coverage. Clinical bile is not brain; quantitative per-sample decision rules require protocol-specific recovery rather than taxon blacklists.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 47 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C48", "text": "Six inference approaches across biomass dilutions compare false sequence/OTU calls; ASV methods improve precision. Sequence inference does not by itself distinguish true low-load tissue biology from contamination.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 48 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C49", "text": "DNase treatment of PCR master mixes reduces measured reagent contamination about 99% in the tested protocol. Kit extraction is not always the largest contaminant source; treatment must preserve assay sensitivity. Online 2018, issue 2019.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 49 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C50", "text": "79 samples from 54 patients include 51 intracranial abscesses, with sequencing detecting broader polymicrobial pathogens. Diagnostic infection is a positive assay control, not evidence of a normal resident human brain community.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 50 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C51", "text": "Nanopore 16S of 27 abscess pus samples detects more anaerobic/polymicrobial findings than culture. Abscess load, inflammation and collection differ from healthy low-biomass brain; detection is not homeostasis.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 51 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C52", "text": "Prospective 20-patient abscess comparison identifies 72 sequenced strains versus 22 culture strains and expands species spectrum. Clinically localized infection establishes microbes can enter brain, without normal residence or neurodegenerative community causality.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 52 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C53", "text": "63 abscess cases yield 18 ISH positives; reported 35% sensitivity/93% specificity versus the composite comparator. Negative ISH cannot exclude all infection, and abscess diagnostic performance cannot establish healthy-tissue assay sensitivity. Online 2024, issue 2025.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 53 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C54", "text": "Two AD brain-derived Chlamydia pneumoniae isolates were cultured through HEp-2 passages and characterized genetically. A substantive viability positive in diseased autopsy tissue; does not establish community residence in living brains, healthy controls or AD necessity.", "carries_number": true, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 54 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C55", "text": "Five AD/five control immunohistological comparisons localize Chlamydia signals near, but not invariably within, amyloid deposits. Proximity and antibody controls do not establish disease ordering, viable community or microbial causation.", "carries_number": false, "load_bearing_for": [ "SC1", "SC2" ], "source_ns": [ 55 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C56", "text": "Human AD gingipain signals accompany inoculated-mouse bacterial load and small-molecule inhibition effects on neurodegenerative readouts. Forced pathogen exposure and protease inhibition are not removal/rescue of an endogenous human resident community.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 56 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C57", "text": "Repeated intravenous P. gingivalis exposure changes BBB transcytosis; Cav/Mfsd-related interventions affect barrier readouts. Installed bacteremia can permit entry; it cannot establish stable homeostatic human residence or sporadic-disease primacy.", "carries_number": false, "load_bearing_for": [ "SC1", "SC3" ], "source_ns": [ 57 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C58", "text": "38-woman placenta culture/qPCR and selected sequencing distinguish surface organisms from internal signals matching blanks/database artifacts. Sterile-tissue comparator highlights contamination control, but placenta absence does not prove adult brain absence.", "carries_number": true, "load_bearing_for": [ "SC2" ], "source_ns": [ 58 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "C59", "text": "Cesarean fetal brain/placenta signals do not exceed controls; isolated C. acnes also occurs in controls while positive controls work. Restricted fetal macaque setting cannot settle adult human brain ecology; a valuable organ/method comparator only.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 59 ], "verification": "verified", "verified_against": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "verified_on": "2026-10-08", "note": "" }, { "id": "CSC1", "text": "Α: orthogonal positive surgical/autopsy signals exist, but no independent viable strain-resolved living-human community replication excludes the demonstrated artifact alternatives. This is an unresolved existence gate, not a finding of universal sterility.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 27, 28, 50, 51, 52, 53, 54, 55, 56, 57 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-08", "note": "" }, { "id": "CSC2", "text": "Β: controls and edge/core comparisons improve specificity, but no complete human case rules out reagent, host, vascular and preanalytic origins together; host-aware null and assay-recovery failures constrain both directions.", "carries_number": false, "load_bearing_for": [ "SC2" ], "source_ns": [ 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 58, 59 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-08", "note": "" }, { "id": "CSC3", "text": "Γ: microbial products and installed infection can change relevant readouts, but resident-human community removal/rescue and neurodegenerative phenotype movement are absent from the examined corpus.", "carries_number": false, "load_bearing_for": [ "SC3" ], "source_ns": [ 1, 6, 21, 22, 23, 28, 56, 57 ], "verification": "verified", "verified_against": "Synthesis of examined primary result/limit cards; framework level is adjudication.", "verified_on": "2026-10-08", "note": "" }, { "id": "CH", "text": "Human brain microbial molecules and occasional viable pathogens are credible possibilities; a reproducible resident community in living human parenchyma, causally driving neurodegeneration, is not established.", "carries_number": false, "load_bearing_for": [ "SC1" ], "source_ns": [ 1, 2, 23, 54, 5 ], "verification": "verified", "verified_against": "Bounded synthesis of examined sources; score is adjudication.", "verified_on": "2026-10-08", "note": "" } ], "citation_ledger": [ { "n": 1, "citation": "Branton WG, Ellestad KK, Maingat F et al. Brain microbial populations in HIV/AIDS: α-proteobacteria predominate independent of host immune status. PloS one. 2013.", "tier": "A", "kind": "primary", "pmid": "23355888", "doi": "10.1371/journal.pone.0054673", "url": "https://pubmed.ncbi.nlm.nih.gov/23355888/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID23355888", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Results:paragraph15, 1:Results:paragraph17, 1:Results:paragraph18, 1:Results:paragraph19, 1:Results:paragraph23, 1:Results:paragraph24, 3:Materials and Methods:paragraph4, 3:Materials and Methods:paragraph5, 3:Materials and Methods:paragraph10. No complete-paper or supplement audit claimed.", "carries_claims": [ "C1", "CSC1", "CSC2", "CSC3", "CH" ] }, { "n": 2, "citation": "Bedarf JR, Beraza N, Khazneh H et al. Much ado about nothing? Off-target amplification can lead to false-positive bacterial brain microbiome detection in healthy and Parkinson's disease individuals. Microbiome. 2021.", "tier": "A", "kind": "primary", "pmid": "33771222", "doi": "10.1186/s40168-021-01012-1", "url": "https://pubmed.ncbi.nlm.nih.gov/33771222/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID33771222", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Methods:paragraph0, 1:Methods:paragraph1, 1:Methods:paragraph15, 1:Methods:paragraph23, 1:Methods:paragraph26, 1:Methods:paragraph28, 2:Results:paragraph2, 2:Results:paragraph15, 2:Results:paragraph16, 2:Results:paragraph18, 2:Results:paragraph20, 2:Results:paragraph24, 2:Results:paragraph27, 2:Results:paragraph31. No complete-paper or supplement audit claimed.", "carries_claims": [ "C2", "CSC1", "CSC2", "CH" ] }, { "n": 3, "citation": "Emery DC, Shoemark DK, Batstone TE et al. 16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer's Post-Mortem Brain. Frontiers in aging neuroscience. 2017.", "tier": "A", "kind": "primary", "pmid": "28676754", "doi": "10.3389/fnagi.2017.00195", "url": "https://pubmed.ncbi.nlm.nih.gov/28676754/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID28676754", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and Methods:paragraph0, 1:Materials and Methods:paragraph5, 1:Materials and Methods:paragraph6, 1:Materials and Methods:paragraph7, 1:Materials and Methods:paragraph11, 3:Discussion:paragraph0, 3:Discussion:paragraph2, 3:Discussion:paragraph3, 3:Discussion:paragraph9. No complete-paper or supplement audit claimed.", "carries_claims": [ "C3", "CSC1", "CSC2" ] }, { "n": 4, "citation": "Emery DC, Davies M, Cerajewska TL et al. High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer's and Parkinson's disease. Frontiers in aging neuroscience. 2022.", "tier": "A", "kind": "primary", "pmid": "36570533", "doi": "10.3389/fnagi.2022.1026260", "url": "https://pubmed.ncbi.nlm.nih.gov/36570533/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID36570533", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C4", "CSC1", "CSC2" ] }, { "n": 5, "citation": "Thwe MN, Moné Y, Sen B et al. Microspatial Heterogeneities and the Absence of Postmortem Contamination in Alzheimer's Disease Brain Microbiota: An Alzheimer's Pathobiome Initiative (AlzPI) Study. Microorganisms. 2025.", "tier": "A", "kind": "primary", "pmid": "40284643", "doi": "10.3390/microorganisms13040807", "url": "https://pubmed.ncbi.nlm.nih.gov/40284643/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID40284643", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:2. Materials and Methods:paragraph0, 1:2. Materials and Methods:paragraph4, 1:2. Materials and Methods:paragraph5, 1:2. Materials and Methods:paragraph6, 2:3. Results and Discussion:paragraph0, 2:3. Results and Discussion:paragraph3, 2:3. Results and Discussion:paragraph4, 2:3. Results and Discussion:paragraph6, 2:3. Results and Discussion:paragraph8. No complete-paper or supplement audit claimed.", "carries_claims": [ "C5", "CSC1", "CSC2", "CH" ] }, { "n": 6, "citation": "Moné Y, Earl JP, Król JE et al. Evidence supportive of a bacterial component in the etiology for Alzheimer's disease and for a temporal-spatial development of a pathogenic microbiome in the brain. Frontiers in cellular and infection microbiology. 2023.", "tier": "A", "kind": "primary", "pmid": "37780846", "doi": "10.3389/fcimb.2023.1123228", "url": "https://pubmed.ncbi.nlm.nih.gov/37780846/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID37780846", "access_depth": "full_text_partial", "access_note": "Complete primary abstract and linked-status metadata examined. Selected body sections: 1:Materials and methods:paragraph0, 1:Materials and methods:paragraph25, 1:Materials and methods:paragraph44, 1:Materials and methods:paragraph49. No complete-paper or supplement audit claimed.", "carries_claims": [ "C6", "CSC1", "CSC2", "CSC3" ] }, { "n": 7, "citation": "Jones TB, Chu P, Wilkey B et al. Regional Differences in Microbial Infiltration of Brain Tissue from Alzheimer's Disease Patients and Control Individuals. Brain sciences. 2024.", "tier": "A", "kind": "primary", "pmid": "39061418", "doi": "10.3390/brainsci14070677", "url": "https://pubmed.ncbi.nlm.nih.gov/39061418/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID39061418", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C7", "CSC1", "CSC2" ] }, { "n": 8, "citation": "Alonso R, Pisa D, Carrasco L et al. Brain Microbiota in Huntington's Disease Patients. Frontiers in microbiology. 2019.", "tier": "A", "kind": "primary", "pmid": "31798558", "doi": "10.3389/fmicb.2019.02622", "url": "https://pubmed.ncbi.nlm.nih.gov/31798558/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID31798558", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C8", "CSC1", "CSC2" ] }, { "n": 9, "citation": "Pisa D, Alonso R, Rábano A et al. Different Brain Regions are Infected with Fungi in Alzheimer's Disease. Scientific reports. 2015.", "tier": "A", "kind": "primary", "pmid": "26468932", "doi": "10.1038/srep15015", "url": "https://pubmed.ncbi.nlm.nih.gov/26468932/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID26468932", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C9", "CSC1", "CSC2" ] }, { "n": 10, "citation": "Alonso R, Pisa D, Aguado B et al. Identification of Fungal Species in Brain Tissue from Alzheimer's Disease by Next-Generation Sequencing. Journal of Alzheimer's disease : JAD. 2017.", "tier": "A", "kind": "primary", "pmid": "28387676", "doi": "10.3233/JAD-170058", "url": "https://pubmed.ncbi.nlm.nih.gov/28387676/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID28387676", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C10", "CSC1", "CSC2" ] }, { "n": 11, "citation": "Pisa D, Alonso R, Fernández-Fernández AM et al. Polymicrobial Infections In Brain Tissue From Alzheimer's Disease Patients. 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Quantifying and Understanding Well-to-Well Contamination in Microbiome Research. mSystems. 2019.", "tier": "A", "kind": "primary", "pmid": "31239396", "doi": "10.1128/mSystems.00186-19", "url": "https://pubmed.ncbi.nlm.nih.gov/31239396/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID31239396", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C46", "CSC2" ] }, { "n": 47, "citation": "Dyrhovden R, Rippin M, Øvrebø KK et al. 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International journal of medical microbiology : IJMM. 2009.", "tier": "A", "kind": "primary", "pmid": "18829386", "doi": "10.1016/j.ijmm.2008.07.002", "url": "https://pubmed.ncbi.nlm.nih.gov/18829386/", "status_flags": [ "none_found" ], "opened": true, "opened_on": "2026-10-08", "status_checked_on": "2026-10-08", "study_id": "PMID18829386", "access_depth": "abstract_metadata", "access_note": "Complete primary abstract and linked-status metadata examined. No complete-paper or supplement audit claimed.", "carries_claims": [ "C54", "CSC1", "CSC2", "CH" ] }, { "n": 55, "citation": "Hammond CJ, Hallock LR, Howanski RJ et al. Immunohistological detection of Chlamydia pneumoniae in the Alzheimer's disease brain. 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